Frontal Baldness Research Articles

Woodhouse-sakati syndrome with no reportable MRI findings: a case report

BackgroundWoodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive condition caused by biallelic pathogenic variants in the DCAF17 gene, with fewer than 200 cases reported in the literature. Symptoms first emerge in middle-late adolescence with a spectrum of hypogonadal and progressive neurological features.Case presentationWe present a case of WSS with no reportable T2-weighted, apparent diffusion coefficient mapping and susceptibility weighted MRI findings. This differs from cases reported in the current literature. Our patient developed abnormal movements in both legs, clumsiness of the hands, dysarthria, and swallowing difficulties. Moreover, she presented with alopecia manifesting as frontal and temporal balding, severe dystonia with painful dystonic spasms primarily in the left upper limb, as well as primary amenorrhea. She was not independently ambulatory on presentation, requiring wheelchair assistance. Genetic testing, the crucial test for a definitive diagnosis, was undertaken in Qatar and confirmed WSS. Treatment provided includes botulinum toxin injections and deep brain stimulation, providing better dystonia control, with progress in walking and strength exercises, and overall remarkable improvement. Intensive neurorehabilitation regimes were also deployed from admission, including physiotherapy, occupational therapy and speech and language therapy.ConclusionThis case adds to the current literature on WSS manifestations, with all previously reported cases having positive MRI findings, unlike our case.

Androgenic Alopecia Is Associated With More Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

To evaluate the possible association between androgenic alopecia (AGA) and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A total of 148 patients aged over 45 with LUTS secondary to BPH were prospectively enrolled in this study. According to the Norwood-Hamilton classification, the patients were divided into two groups: AGA (n = 69) and non-AGA (n = 79). In addition, the cases of AGA were categorized as vertex (n = 39) and frontal baldness (n = 30). The International Prostate Symptom Score (IPSS), uroflowmetry parameters, prostate volume, serum total testosterone (TT), and free and total prostate-specific antigen concentrations of all patients were assessed and compared between the groups. Correlations between the AGA grade and other variables were also investigated. The serum TT level (354 ± 97.1 vs. 308.6 ± 73.1 ng/dL, p = 0.01), total IPSS (16.1 ± 8.1 vs. 13.4 ± 7.7, p = 0.04), IPSS storage subscore (IPSS-S) (7.1 ± 3.5 vs. 5.8 ± 3.6, p = 0.03), and number of nocturia episodes (2.5 ± 1.4 vs. 1.8 ± 1.4, p < 0.01) were significantly higher in the AGA group than in the non-AGA group. There were no significant differences in any of the parameters between the patients with vertex and frontal baldness. The AGA grade showed a significant positive correlation with the TT level (r = 0.407, p = 0.003), IPSS-S (r = 0.164, p = 0.04), and number of nocturia episodes (r = 0.203, p = 0.015). This study demonstrated that among patients with LUTS, those with AGA had worse symptoms and higher TT levels compared with those without AGA of similar age. Furthermore, the AGA grade was positively correlated with the TT level and storage symptoms.

Myotonic dystrophy type 1: 13 years of experience at a tertiary hospital. Clinical and epidemiological study and genotype-phenotype correlation

IntroductionThe incidence of myotonic dystrophy type 1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). MethodsRetrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5–35), premutation (36–50), protomutation (51–80), small expansions (81–150), intermediate expansions (151–1000), and large expansions (> 1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5–50 CTG repeats), mild form or asymptomatic (51–150), classical form (151–1000), and severe form (> 1000). ResultsThe incidence of DM1 was 20.61 cases per million person-years (95% CI, 19.59–21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = –0.547; 95% CI, –0.610 to –0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. ConclusionsThe incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

PMON224 Newly Observed Interference of Oral Biotin with the Free Testosterone Assay? In a Woman with Postmenopausal Virilization.

Abstract Introduction Approximately 15-20% of US adults take supraphysiologic doses of biotin-containing supplements for common hair and skin problems. When consumed in high doses, competitive and non-competitive immunoassays which use the streptavidin-biotin binding complex can skew results to be either falsely high or falsely low. Case Presentation A 74 y/o Caucasian female who initially presented to her primary care physician concerned for alopecia with frontal balding, acne and moderate hirsutism. Her total testosterone was elevated with 146 ng/dL (7.0–40 ng/dL) with a perplexing normal free testosterone of 4.2 pg/mL (&amp;lt;4.2 pg/mL) in the context of a normal SHBG of 48 nmol/L (14–73 nmol/L). Androstenedione was elevated with 161 ng/dL (17–99 ng/dL) with a normal CMP, prolactin, DHEA-s and 17-hydroxyprogesterone. Transvaginal US was normal. The size of the ovaries was consistent with menopause. Abdominal and pelvic MRI showed normal adrenal glands and ovaries. She was taking between 1 to 3mg of biotin per day. Biotin was discontinued. Repeat testing revealed an elevated free testosterone of 12.7 pg/mL (0.2 - 3.7 pg/mL) along with an elevated total testosterone of 120 ng/dL (2 - 45 ng/dL) and a normal SHBG of 39 nmol/L (14–73 nmol/L) which was now consistent with her clinical picture of postmenopausal hyperandrogenism. Bilateral laparoscopic salpingo-oophorectomy was recommended to exclude an androgen-secreting ovarian tumor or hyperthecosis. Testing was then repeated while taking biotin which again manifested a normal free testosterone of 2.8 pg/mL (&amp;lt;4.2 pg/mL) with an elevated total testosterone of 121.4 ng/dL (7.0–40 ng/dL) and a normal SHBG of 45 nmol/L (14–73 nmol/L). Discussion Biotin may interfere with the total testosterone levels, but little is known of its effects on free testosterone. We report the first case of biotin interference on the free testosterone assay, resulting in falsely low values demonstrated in two different occasions, that improved following withdrawal of this widely used vitamin supplement. Laboratories use a direct analog enzyme immunoassay to calculate the free testosterone however its calibration and specificity has been debatable, and it is still unclear how biotin can affect it. It is critical that laboratorians and clinicians are aware of this biotin interference so that misdiagnosis and inappropriate treatment can be prevented.

Expanded CUG Repeat RNA Induces Premature Senescence in Myotonic Dystrophy Model Cells.

Myotonic dystrophy type 1 (DM1) is a dominantly inherited disorder due to a toxic gain of function of RNA transcripts containing expanded CUG repeats (CUGexp). Patients with DM1 present with multisystemic symptoms, such as muscle wasting, cognitive impairment, cataract, frontal baldness, and endocrine defects, which resemble accelerated aging. Although the involvement of cellular senescence, a critical component of aging, was suggested in studies of DM1 patient-derived cells, the detailed mechanism of cellular senescence caused by CUGexp RNA remains unelucidated. Here, we developed a DM1 cell model that conditionally expressed CUGexp RNA in human primary cells so that we could perform a detailed assessment that eliminated the variability in primary cells from different origins. Our DM1 model cells demonstrated that CUGexp RNA expression induced cellular senescence by a telomere-independent mechanism. Furthermore, the toxic RNA expression caused mitochondrial dysfunction, excessive reactive oxygen species production, and DNA damage and response, resulting in the senescence-associated increase of cell cycle inhibitors p21 and p16 and secreted mediators insulin-like growth factor binding protein 3 (IGFBP3) and plasminogen activator inhibitor-1 (PAI-1). This study provides unequivocal evidence of the induction of premature senescence by CUGexp RNA in our DM1 model cells.

Cellular Senescence and Aging in Myotonic Dystrophy.

Myotonic dystrophy (DM) is a dominantly inherited multisystemic disorder affecting various organs, such as skeletal muscle, heart, the nervous system, and the eye. Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by expanded CTG and CCTG repeats, respectively. In both forms, the mutant transcripts containing expanded repeats aggregate as nuclear foci and sequester several RNA-binding proteins, resulting in alternative splicing dysregulation. Although certain alternative splicing events are linked to the clinical DM phenotypes, the molecular mechanisms underlying multiple DM symptoms remain unclear. Interestingly, multi-systemic DM manifestations, including muscle weakness, cognitive impairment, cataract, and frontal baldness, resemble premature aging. Furthermore, cellular senescence, a critical contributor to aging, is suggested to play a key role in DM cellular pathophysiology. In particular, several senescence inducers including telomere shortening, mitochondrial dysfunction, and oxidative stress and senescence biomarkers such as cell cycle inhibitors, senescence-associated secretory phenotype, chromatin reorganization, and microRNA have been implicated in DM pathogenesis. In this review, we focus on the clinical similarities between DM and aging, and summarize the involvement of cellular senescence in DM and the potential application of anti-aging DM therapies.

Social cognition in type 1 myotonic dystrophy – A mini review

Our ability to interact with those around us plays an important role in our relationships, mental well being and ability to successfully navigate the complex social society in which we live. Research in social cognitive neuroscience aims to understand the underlying neurobiology of our social behaviours and interactions with others. Myotonic dystrophy type 1 (DM1) is a genetically inherited neuromuscular disorder characterized by mytonia with systemic manifestations such as cardiac disease, respiratory insufficiency, ophthalmic complications, diabetes and frontal balding among others. Individuals with myotonic dystophy have been found to have widespread changes throughout the brain in both grey and white matter territories. They have been noted to experience difficulty with social cognitive function, and to more frequently display atypical personality traits leading to often unrecognized difficulties with everyday life. In this mini review we explore the anatomical basis of social cognition, current techniques for measuring and investigating this impairment including facial emotion recognition and theory of mind. We examine the evidence for general cognitive dysfunction, autism spectrum and personality disorders in DM1. Throughout the review we discuss neuroimaging highlights relevant to social cognition in DM1. Finally, we discuss practical implications relevant to managing people with myotonic dystrophy and highlight future research needs.

Distrofia miotónica tipo 1: 13 años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo

IntroductionThe incidence of myotonic dystrophy type1 (DM1), a disease with great phenotypic variety, in our region is unknown. This study aims to estimate the incidence of DM1 at our hospital (a reference centre in Aragon, Spain) and to identify the characteristics of our population (genotype-phenotype correlation). MethodsRetrospective, descriptive study of 459 patients classified according to the number of CTG repeats, as follows: normal (5-35), premutation (36-50), protomutation (51-80), small expansions (81-150), intermediate expansions (151-1000), and large expansions (>1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (>1000). ResultsThe incidence of DM1 was 20.61 cases per million person-years (95%CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ=−0.547; 95%CI: −0.610 to −0.375; P<.001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. ConclusionsThe incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management.

Presentation of ACTH Independent Cushing’s as Severe Insulin Resistance During Pregnancy

Introduction: Cushing’s syndrome is very rare in pregnancy with around 200 cases reported in literature. It remains a diagnostic dilemma as pregnancy itself is a hypercortisolemic state. Several clinical characteristics of Cushing’s syndrome such as insulin resistance and hirsutism may overlap with normal variants of pregnancy and therefore leading to a missed diagnosis. We hereby present a case of a young pregnant woman with severe insulin resistance, with workup consistent with Cushing’s syndrome. Clinical Case: This was a 27-year-old pregnant woman with DM type 2 diagnosed about 7 years ago. During her pregnancy she was started on insulin and was later admitted to the hospital at 32 weeks for inpatient management of pre-eclampsia and uncontrolled hyperglycemia. Endocrine was consulted for severe insulin resistance and persistent hyperglycemia. On exam patient was noted to be obese with facial plethora, frontal balding and significant facial hirsutism. During the pregnancy she had noted significant weight gain with substantial worsening of frontal balding and hirsutism. Her current pregnancy was spontaneous but was after many years of trying to conceive. Prior pregnancy 8 years ago was uncomplicated with no history for GDM at that time. Review of recent pre-pregnancy imaging revealed left adrenal mass measuring 3.5 cm with 40 HU which measured around 2 cm 8 years ago. Biochemical work up revealed elevated 8 am cortisol at 35.4 ug/dL (ref range 6.2 - 19.4) with suppressed ACTH <5 pg/mL (6 – 50). Testosterone was high at 299 ng/dL (8 – 48) and DHEAS was low normal at 37 mcg/dL (18 – 391). Plasma and 24 hour urine metanephrine collection results were normal. 24-hour urine free cortisol was measured and was elevated at 628.5 mcg/24(4.0–50.0). Midnight salivary cortisol was 0.87 mcg/dL (<OR=0.09). Patient was managed conservatively with plan for surgical intervention post-delivery. Pregnancy was complicated by PPROM at 35 weeks with subsequent cesarean section. Baby was of average weight but developed mild hyperbilirubinemia which required short NICU stay. On reevaluation at 4-week postpartum period, repeat biochemical workup revealed elevated cortisol of 22.5 mcg/dL, ACTH <5 pg/ml, elevated 24-hour urine cortisol 163.9 mcg/24h with appropriate urinary creatinine. Testosterone level was improved postpartum to 9 ng/dL. DHEAS was 39 mcg/dL. Repeat imaging with CT with adrenal protocol revealed left adrenal mass measuring 2.3 cm with 20 HU with absolute washout of 79%. She was started on ketoconazole is now awaiting surgical intervention. Conclusion: We suspect that this patient may have had pregestational subclinical Cushing’s syndrome which eventually progressed to Cushing’s syndrome during pregnancy. Although this is a rare finding during pregnancy, workup for Cushing’s should be considered in pregnant women with severe insulin resistance, hirsutism, hypertension and pre-eclampsia.

Ectopic Adrenal Tumor in a Patient With Untreated Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Case Presentation: A 43 year-old female was diagnosed at birth with non-salt wasting congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and underwent clitoral reduction surgery. She was treated with hydrocortisone and had menarche at age 7 with irregular and heavy menses. At age 15 she had a D&C with removal of “something in her ovaries.” She stopped hydrocortisone at age 30 except for stress doses during illness. At age 35 she stopped oral contraceptives and thereafter has been amenorrheic. She presented with abdominal distention and constipation. On exam she had short stature, marked frontal and temporal balding, hirsutism, increased musculature and a large distended abdomen. Labs showed AM cortisol 3.1 mcg/dL (nl 10–20), ACTH 440 pg/ml (nl <46), 17-OH Progesterone 11000 ng/dL (nl <206), DHEAS 362 mcg/dl (nl <430), FSH 0.2 mIU/ml, LH 2.7 mIU/ml, testosterone 618 ng/dl (nl 10–75), and estradiol 162 pg/ml (nl post menopause <41). MRI showed a massive fibroid (30 cm), bilateral adrenal hyperplasia and a left paraaortic, retroperitoneal mass (5.9 cm). She underwent hysterectomy with removal of a 9.5 kg uterus containing degenerated fibroids, left adrenalectomy and removal of the left paraaortic mass that was initially read as oncocytic adrenal cortical neoplasm, metastatic. A similar oncocytic neoplasm was noted in the left adrenal gland and on further review with pathology the revised report read paraaortic mass, probable adrenal rest tumor. Discussion: Excess androgens and chronically elevated ACTH levels in untreated CAH can lead to adverse effects beyond adrenal insufficiency and virilization. We present a woman with untreated classic CAH who developed a large fibroid and paraaortic adrenal cortical tumor. Fibroids have been described in CAH patients, a potential consequence of elevated androgens that are converted by aromatase in the endometrium to estrogens driving growth of fibroid tumors. Chronic ACTH can further act as a growth factor, leading to adrenal hyperplasia, adrenal tumors and ectopic adrenal rest tissue. Intra-adrenal tumors in untreated CAH are generally benign with rare cases of adrenal cortical carcinoma reported.Ectopic adrenal rest tissue in untreated CAH is most commonly reported in testes. There have been rare case reports of ectopic adrenal rest tumors in the adnexa, broad ligament, and perirenal area. Our patient presents as an unusual case of ectopic adrenal rest tumor in the paraaortic region. Based on the atypical location and incomplete history available to the pathologist, it was initially read as metastatic adrenocortical carcinoma. Upon further review given the clinical information, the diagnosis was revised to indicate a pararenal adrenal rest tumor. This case highlights the importance of glucocorticoid compliance in CAH and the necessity to provide a clinical context for the pathologist in cases of extra-adrenal tumors in untreated CAH.

Invasive giant pituitary macroadenoma causing Cushing disease; a case report

Introduction: Cushing disease is a rare entity, and among them, giant pituitary adenomas causing Cushing disease is rarer. Here we present a case of Cushing disease secondary to a giant pituitary macroadenoma. Case report: A 41-year-old female with poorly controlled diabetes mellitus and hypertension diagnosed for six months presented with a history of unintentional weight loss, polyuria and polydipsia for the same duration. There was change in her facial appearance with increased pigmentation, frontal balding and she also noted increase in the size of her abdomen. There were features of proximal muscle weakness. Symptoms of hypothyroidism, hypoadrenalism or hyperprolactinemia were absent, and she was amenorrhoeic following hysterectomy done a year back. Visual impairment, headache, abdominal pain, features suggestive of internal malignancy, especially lung and renal, including features of pheochromocytoma were absent. She denied a family history of similar illness. Her BMI was 20.44 kg/m–2. She had a prominent abdomen, round facies, hirsutism, male pattern hair loss, facial plethora and generalized pigmentation and thinning of skin. She also had hypertension and proximal muscle weakness. Rest of the examination was normal. Investigations revealed hypokalaemia, poorly controlled hyperglycaemia and, non-suppressed overnight dexamethasone suppression test. She had a elevated ACTH level, and a high dose dexamethasone suppression test showed suppression. Pituitary imaging with MRI revealed a 51x 62x 41 mm size sellar and a para sellar mass with heterogeneous echogenicity extending to the right temporal lobe. Further imaging for ectopic ACTH secretion was negative.She underwent transcranial surgery which was unsuccessful due to intraoperative bleeding, and radiotherapy was given postoperatively. Conclusion: Cushing disease due to giant pituitary macroadenomas are rare and may require secondary therapeutic measures in controlling the disease in case of failed surgery.

An adolescent girl with coexisting ovarian mature cystic teratoma and HAIR-AN syndrome, an extreme subtype of polycystic ovarian syndrome.

SummaryPolycystic ovarian syndrome (PCOS) is associated with menstrual irregularities, ovulatory dysfunction, hirsutism, insulin resistance, obesity and metabolic syndrome but is rarely associated with severe hyperandrogenaemia and virilisation resulting in male pattern baldness and clitoromegaly. Total serum testosterone greater than twice the upper limit of the reference range or free androgen index of over five-fold elevated suggests a diagnosis other than PCOS. We reported a case of a 15 years old obese girl presented with secondary amenorrhoea, virilising signs: frontal baldness, clitoromegaly and prominent signs of insulin resistance and marked acanthosis nigricans. Her total testosterone level was markedly elevated at 9.4 nmol/L (0.5–1.7 nmol/L) and MRI pelvis revealed a right ovarian mass with fat and cystic component and a left polycystic ovary. The patient underwent laparoscopic right ovarian cystectomy and histologically confirmed mature cystic teratoma. Post-operatively, her testosterone level declined but did not normalise, menses resumed but remained irregular. Her fasting insulin was elevated 85.2 mIU/L (3–25 mIU/L) and HOMA-IR was high at 13.1 (>2) with persistent acanthosis nigricans suggesting co-existing HAIR-AN syndrome, an extreme phenotype of polycystic ovarian syndrome.Learning pointsRapid onset of hyperandrogenic symptoms, especially if associated with signs of virilisation must raise the suspicion of an androgen-secreting tumour.Total serum testosterone greater than twofold the upper limit of the reference range or free androgen indices over fivefold suggest a diagnosis other than polycystic ovarian syndrome (PCOS).High levels of testosterone with normal levels of the DHEA-S suggest an ovarian source.Ovarian androgen-secreting tumour and HAIR-AN syndrome, an extreme spectrum of PCOS can co-exist.

Non-alcoholic fatty liver disease later diagnosed as myotonic dystrophy

BACKGROUNDMyotonic dystrophy (MD) is sometimes accompanied by metabolic/endocrine disorders, including dyslipidemia, central obesity, and hypogonadism. Due to considerable individual differences in the severity and progression of myopathy, MD patients with minimal-to-mild muscle symptoms might be followed as having other diseases, such as non-alcoholic fatty liver disease (NAFLD).CASE SUMMARYA 40-year-old non-obese man without a history of regular ethanol consumption was referred to our hospital due to persistent liver dysfunction and hyperlipidemia. His body mass index was 23.4 kg/m2. Liver histology demonstrated macrovesicular steatosis, ballooned hepatocytes with eosinophilic inclusion bodies, and perisinusoidal fibrosis, leading to the diagnosis of non-alcoholic steatohepatitis (NASH). Although he had no discernable muscle pain or weakness, persistently high serum creatine kinase (CK) and myoglobin levels as well as the presence of frontal baldness, a hatched face, history of cataract surgery, and grip myotonia indicated the possibility of MD. Southern blotting of the patient’s DNA revealed the presence of CTG repeats, confirming the diagnosis.CONCLUSIONWhen gastroenterologists encounter NAFLD/NASH patients, serum CK should be verified. If hyperCKemia, frontal baldness, a hatched face, history of cataract surgery, and grip myotonia are noted, the possibility of MD may be considered.

Baldness and Risk of Prostate Cancer in the Health Professionals Follow-up Study.

The association between male pattern baldness and prostate cancer has been inconsistent. We prospectively investigated the association between baldness at age 45 and prostate cancer risk in the Health Professionals Follow-up Study (HPFS), focusing on clinical and molecular markers. Baldness was self-reported on the 1992 questionnaire using the modified Norwood-Hamilton scale prior to diagnosis. We estimated HRs between baldness and prostate cancer risk among 36,760 men, with follow-up through 2014. We also investigated whether baldness was associated with prostate cancer defined by tumor protein expression of androgen receptor and the presence of the TMPRSS2:ERG fusion. During 22 years, 5,157 prostate cancer cases were identified. Fifty-six percent of the men had either frontal or vertex baldness. No significant associations were found between baldness and prostate cancer risk. Among men younger than 60 years, there was a statistically significant association between frontal and severe vertex baldness and overall prostate cancer (HR: 1.74; 95% confidence interval: 1.23-2.48). Baldness was not significantly associated with expression of molecular subtypes defined by AR and TMPRSS2:ERG IHC of prostate tumors. This study showed no association between baldness at age 45 and prostate cancer risk, overall or for clinical or molecular markers. The association between baldness and overall prostate cancer among younger men is intriguing, but caution is warranted when interpreting this finding. The null findings from this large cohort study, together with previous literature's inconclusive findings across baldness patterns, suggest that baldness is not a consistent biomarker for prostate cancer risk or progression.

SAT-510 Association of Myotonic Dystrophy with Autoimmune Endocrinopathies and Thyroid Carcinoma

Myotonic dystrophy (MD) is a multisystemic, autosomal dominant disorder associated with progressive muscle weakness, premature cataracts, frontal baldness, and cardiac disturbances. MD has been associated with several endocrinopathies including primary testicular failure, autoimmune endocrinopathies (hypothyroidism, hyperthyroidism, multinodular goiter, and Addison’s disease), thyroid carcinoma (primarily papillary), insulin resistance, and type 2 DM. Development of diabetes is thought to be related to formation of an insulin-resistant receptor because of aberrant regulation of mRNA. We describe the first reported case of a patient with MD associated with type I diabetes mellitus, Hashimoto’s thyroiditis with hypothyroidism, and follicular variant of papillary thyroid cancer. A 49-year-old female presented with acute congestive heart failure. The patient had history of type I DM diagnosed at the age of 26, complicated by mild background retinopathy, peripheral neuropathy, and nephropathy with microalbuminuria. The patient first noticed proximal muscle weakness 1 year ago that gradually progressed resulting in multiple falls. She had history of bilateral cataracts status post cataract extraction at age 26. She also had progressive dysphagia requiring PEG placement, and cognitive dysfunction with mood disorder and depression. Family history was significant for myotonic dystrophy in both maternal aunt and uncle as well as 2 cousins. EMG confirmed myotonia however genetic testing was not obtained due to cost. Due to her cognitive dysfunction and depression, she had difficult to control diabetes with HbA1c of 9.9%, and multiple previous admissions for DKA. She was status post total thyroidectomy in 2008 for follicular variant of papillary carcinoma and Hashimoto’s thyroiditis followed by I-131 therapy in 2009 and maintained on levothyroxine suppression therapy. Most recent Tg and Tg Ab were undetectable. On physical exam, the patient had a narrow, sallow face with temporal muscle atrophy, percussion myoclonus involving the thenar eminence of the hands, but no frontal balding. Work up showed LVEF of 20-24% with regional hypokinesis that led to catherization and PCI to LAD. The patient had recurrent NSTEMI which eventually resulted in CABG 1 year after presentation. The association of autoimmune endocrinopathies, thyroid carcinoma and MD suggests a possible cause and effect relationship between these disorders. In patients with diabetes and MD, previously described insulin resistance as well as cognitive dysfunction can hinder good glycemic control increasing risk for complications. Although patients with MD are typically treated by neurologists, evaluation and therapy of endocrine dysfunctions are also necessary.

Multisystemic Impairments in 93 Chinese Patients With Myotonic Dystrophy Type 1.

Background: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease characterized by muscle weakness and multisystemic impairments, which significantly impact the quality of life. There is currently an increasing consensus on the necessity of a multidisciplinary assessment in patients with DM1, to improve the management of the disease.Methods: To analyze the prevalence and pairwise relationships between various organs involved, we performed a retrospective study by reviewing demographic and clinical information of DM1 patients including age, disease duration, clinical history, muscular impairment rating scale score (MIRS), results of blood biochemistry, electrocardiogram, echocardiography, and ophthalmologic examination.Results: Ninety three DM1 patients (60 males and 33 females), aged 34.7 ± 12.6 (mean ± standard deviation) years were recruited. Of which, two congenital cases were of maternal and paternal inheritance, respectively. In the other 91 patients, cataract was found in 44.1% of patients, followed by hypogonadism (40.8%), frontal balding (40.7%), and cardiac abnormalities (34.5%). Thyroid dysfunction and insulin insensitivity were relatively uncommon. Age (p < 0.001) is independently correlated with cataract, and MIRS correlates positively with cardiac abnormalities (p = 0.005) and frontal balding (p = 0.015). Male patients more frequently had frontal balding (Risk ratio, 3.98; 95% confidence interval, 1.493–10.611) compared with female patients. Male patients with cataract presented more frequent cardiac abnormalities (Risk ratio, 4.40; 95% confidence interval, 1.055–18.358) compared with non-cataract male patients. Hypogonadism in male patients was characterized as decreased testosterone level, accompanied by elevated levels of luteinizing hormone and follicle-stimulating hormone.Conclusions: In Chinese patients with DM1, we conclude that (1) cataract, hypogonadism, frontal balding and cardiac abnormalities are frequently observed; (2) age is an independent indicator to cataract and MIRS is the only predictor for cardiac abnormalities and frontal balding; (3) a positive correlation between ophthalmologic and cardiac impairments in male patients is found; (4) endocrine abnormalities show diverse manifestations and hormone tests are recommended; (5) particular attention should be given to patients with older age and higher MIRS score.

SUN-208 Rare Case of 47XXY/46XX Mosaic Klinefelter Syndrome

Introduction: Klinefelter syndrome (KS) is the most common X chromosome abnormality and genetic cause of male infertility. Nondisjunction of paired X chromosomes during meiosis or gametogenesis gives rise to the karyotype 47XXY seen in 80 % of cases. The most common form of mosaicism results from post-fertilization nondisjunction of the XXY zygote in two cell lines 47XXY/46XY in 15-20 % of KS. The 47XXY/46XX mosaic form is very rare with only 20-25 cases described in the literature to date. Phenotype varies with distribution of the two cell lineages in developing embryo tissues, including KS male, true hermaphroditism, ovarian hypoplasia and normal female. Only 10 cases have been reported of 47XXY/46XX mosaic KS male phenotype . Our case is the 11th. Case: A 39 year old male presented with fatigue, weight gain, poor concentration and loss of libido. He reported no secondary sexual development during puberty, including hair, muscle mass, penis and testicles, and minimal erections. On exam, both testes were less than 2 cm with a normal penis. He had abdominal obesity, reduced muscle mass, and gynecomastia, as well as male pattern frontal baldness. Total testosterone (T) was 125 ng/dl (250-1100), Free T was 16 ng/dl (46-224), albumin was 3.9, FSH was 25 mIU/ml, and LH was 15.9 mIU/ml. Chromosome analysis: 25/30 (83%) cells 47XXY and 5/30 (17 %) cells 46XX. FISH study on 100 peripheral blood cells showed 87 % 47XXY and 14 % 46XX. The patient did not desire fertility and started testosterone replacement. Conclusion: Our case demonstrated the common features of 47XXY/46XX mosaic KS, including small testes, gynecomastia, hypergondotropic hypogonadism, and normal IQ. Interestingly, our patient had male pattern baldness, which was also common in his family. The average age of diagnosis for cases reported to date was 12-62 years, similar to ours, suggesting a delay in diagnosis, as can occur in many KS cases. Distribution of cell lines can vary between different tissues, but the presence of a Y chromosome in the gonad determines the phenotype. Mediastinal germ cell tumor, testicular teratoma, and radioulnar synostosis have been noted in 3 cases but not in this case. Mosaic cases tend to be more androgenic, and are more likely to have spermatogenesis than non-mosaic KS. This along with the failure to detect the 46XX cell line in routine blood cytogenetic tests (as opposed to gonadal tissue) is the reason for delayed detection in many cases. KS mosaicism should be considered in all cases of male infertility.

Myotonic Dystrophy-A Progeroid Disease?

Myotonic dystrophies (DM) are slowly progressing multisystemic disorders caused by repeat expansions in the DMPK or CNBP genes. The multisystemic involvement in DM patients often reflects the appearance of accelerated aging. This is partly due to visible features such as cataracts, muscle weakness, and frontal baldness, but there are also less obvious features like cardiac arrhythmia, diabetes or hypogammaglobulinemia. These aging features suggest the hypothesis that DM could be a segmental progeroid disease. To identify the molecular cause of this characteristic appearance of accelerated aging we compare clinical features of DM to “typical” segmental progeroid disorders caused by mutations in DNA repair or nuclear envelope proteins. Furthermore, we characterize if this premature aging effect is also reflected on the cellular level in DM and investigate overlaps with “classical” progeroid disorders. To investigate the molecular similarities at the cellular level we use primary DM and control cell lines. This analysis reveals many similarities to progeroid syndromes linked to the nuclear envelope. Our comparison on both clinical and molecular levels argues for qualification of DM as a segmental progeroid disorder.

Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank

Incidence of upper gastrointestinal cancers of the oesophagus and stomach show a strong unexplained male predominance. Hormonal and reproductive factors have been associated with upper gastrointestinal cancers in women but there is little available data on men. To investigate this, we included 219,425 men enrolled in the UK Biobank in 2006-2010. Baseline assessments provided information on hormonal and reproductive factors (specifically hair baldness, number of children fathered, relative age at first facial hair and relative age voice broke) and incident oesophageal or gastric cancers were identified through linkage to U.K. cancer registries. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During 8 years of follow-up, 309 oesophageal 210 gastric cancers occurred. There was some evidence that male pattern baldness, was associated with gastric cancer risk (adjusted HR 1.35, 95% CI 0.97, 1.88), particularly for frontal male pattern baldness (adjusted HR 1.52, 95% CI 1.02, 2.28). There was little evidence of association between other hormonal and reproductive factors and risk of oesophageal or gastric cancer, overall or by histological subtype. In the first study of a range of male hormonal and reproductive factors and gastric cancer, there was a suggestion that male pattern baldness, often used as a proxy of sex hormone levels, may be associated with gastric cancer. Future prospective studies that directly test circulating sex steroid hormone levels in relation to upper gastrointestinal cancer risk are warranted.

Possible association between androgenic alopecia and risk of prostate cancer and testicular germ cell tumor: a systematic review and meta-analysis

BackgroundA number of studies have investigated the association between androgenic alopecia (AGA) and cancer risk, but they have yielded inconsistent results. Therefore, this study was conducted to explore this controversial subject.MethodsA literature database search was performed according to predefined criteria. An odds ratio (OR) or a hazard ratio (HR) with 95% confidence intervals (CIs) was retained to evaluate the relationship between the incidence of cancer or cancer-specific mortality and categories of AGA. Then a pooled OR or HR was derived.ResultsThe pooled results showed that no specific degree of baldness had an influence on the incidence of cancer or cancer-specific mortality. However, AGA, especially frontal baldness, with the incidence of testicular germ cell tumor (TGCT) (OR = 0.69; 95% CI = 0.58–0.83). A significant increase of risk was observed in relation to high grade prostate cancer (PC) (OR = 1.42; 95% CI 1.02–1.99) and vertex with/without frontal baldness was associated with PC risk.ConclusionsThe study results supported the hypothesis that AGA is negatively associated with TGCT risk and suggested an overlapping pathophysiological mechanism between them, while the viewpoint that AGA can be used as a phenotypic marker for PC risk was poorly supported.