Normal Thyroid Hormone Levels Research Articles

Isolated growth hormone deficiency and amenorrhea – Case report

Growth hormone (GH) deficiency is the most common hypopituitarism disorder. We highlight the challenges to its diagnosis and management in the setting of a developing country. A 14-year-old came with a chief complaint of inability to menstruate. Menarche was at 12-years old, lasted 7 days, soaking 2 pads/day which discontinued shortly after. Thelarche was at 12-years-old and her breast is at Tanner stage 3. Her axillary and pubic hair are at Tanner stage 1. Height was 120 cm, weight 34.8 kg, height for age z-score<-3. Her lab results were normal for estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. Bone age was suitable for age. Magnetic resonance imaging revealed pituitary gland hypoplasia (5.3 mm). A hormonal panel 3 years prior showed abnormally low GH level but normal cortisol and thyroid hormone levels. She was diagnosed with isolated growth hormone deficiency (IGHD) with delayed puberty. She was treated with medroxyprogesterone tablets once daily, after which her menstruation restarted. However, due to her economic background, she declined genetic tests, discontinued her medication and amenorrhea recurred. Amenorrhea present after a brief menarche should alert gynaecologists of a possible multi-hormone disorder with an underlying structural abnormality. IGHD may be due to a structural abnormality, such as pituitary gland hypoplasia. Unfortunately, economic reasons prevented the patient from receiving optimal treatment. IGHD rarely presents with a gynaecological complaint. Hormonal and genetic tests along with imaging should be undertaken. Growth hormone supplementation is the treatment of choice.

LBODP104 Thyroid Plasmapheresis: An Alternative Option For Thyroid Storm

Abstract Introduction Thyroid storm is a rare, life-threatening condition with a high mortality rate approaching 10-30%. The mainstay of treatment includes initiation of therapy directed against the thyroid, supportive intensive care, and treatment of any precipitating factors. We report three cases of patients with thyroid storm and successful therapeutic use of plasmapheresis when traditional therapy was contraindicated. Clinical Cases Case 1 A 22-year-old male with no known past medical history, presented with fever, shortness of breath, and syncope. Labs showed TSH 0. 014 mIU/L (range 0.4-4.5), FT4 4.30 ng/dL (range 0.9-2.2), TSI 546% (range &amp;lt;140), and TPO 20 U/mL (range &amp;lt;60). He was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 60). He was initially treated with propylthiouracil (PTU), hydrocortisone, propranolol, and Lugol's iodine solution. He developed transaminitis and shock liver so was not able to continue PTU or trial methimazole. He underwent 4 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Case 2 A 37-year-old female with known Graves’ disease (non-adherent to antithyroid drug), presented with shortness of breath and palpitations. Labs showed TSH &amp;lt;0. 01 mIU/L (range 0.4-4.5), FT4 4.83 ng/dL (range 0.9-2.2), and FT3 6. 0 pg/mL (range 2.3-4.2). Burch-Wartofsky score was 40 and supported the diagnosis of thyroid storm. She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed transaminitis and there was also concern for methimazole-induced insulin autoimmune syndrome, so methimazole was discontinued. She underwent 3 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Case 3 A 31-year-old female with no known past medical history, presented with shortness of breath and altered mental status requiring intubation. Labs showed TSH &amp;lt;0. 01 mIU/L (range 0.4-4.5), FT4 4.65 ng/dL (range 0.9-2.2), FT3 25.2 pg/mL (range 2.3-4.2), TSI 467% (range &amp;lt;140), TPO 375 U/mL (range &amp;lt;60). She was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 90). She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed pulmonary alveolar hemorrhage and it was unclear if this was due to methimazole, thus methimazole was discontinued. She underwent 5 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Conclusion Plasmapheresis can be an effective and safe treatment option in thyroid storm when there are contraindications for antithyroid drugs or when rapid normalization of thyroid hormone levels is needed. It should be considered as a stabilizing measure as it leads to marked improvement of thyrotoxicosis within 3-5 days, allowing thyroidectomy for definitive therapy. Presentation: No date and time listed

ODP079 BCG-Osis, a Rare Cause of 1,25 Hydroxy Vitamin D Mediated Hypercalcemia

Abstract Background Non-parathyroid hormone (PTH) mediated hypercalcemia is mostly related to malignancy and less commonly caused by granulomatous diseases. We report a rare case of severe hypercalcemia caused by systemic granulomatous disease after intravesical Bacillus Calmette-Guerin (BCG) treatment for bladder cancer (BCGosis). Clinical Case 74-year-old male with history of bladder cancer treated with intravesical BCG a year ago, was hospitalized with confusion, weakness, recurrent falls and polyuria for a few days. He had night sweats and 50 lb weight loss over 6 months. Lab evaluation showed hypercalcemia with calcium 10.9 mg/dL, albumin 3.6 g/dL, corrected calcium 11.2 mg/dL, PTH 12 pg/ml, and 25 OH vitamin D 44ng/ml. He had normal thyroid hormone levels, serum electrophoresis and PTHrP &amp;lt;2 pmol/L. CT chest/abdomen/pelvis without contrast revealed sub-cm pulmonary nodules and non-obstructive renal calculi and bone scan showed no evidence of osseous metastases. He was treated with intravenous (IV) hydration and pamidronate 60 mg infusion, and his corrected calcium improved to 9.7 mg/dL. He was admitted again 3 weeks later with hypercalcemia, calcium 11.9 mg/DL, albumin 3.2 g/dL, corrected calcium 12.5 mg/dL, 25 OH vitamin D 24 ng/ml, PTH 14.6 pg/ml, and PTHrP &amp;lt;2 pmol/L. He received IV hydration and zoledronic acid 4 mg infusion. 3 weeks later he was hospitalized for the third time for recurrent hypercalcemia and worsening renal failure, calcium 13.2, albumin 2.6 g/dL, corrected calcium 14.2 mg/dL, PTH 19.2 pg/ml. 1,25 OH vitamin D checked this time was elevated at 113 pg/mL. He received another infusion of zoledronic acid 4 mg infusion and 10 days later required denosumab 120 mg for resistant hypercalcemia. PET CT scan showed multiple hypermetabolic foci in right neck, right anterior 4th rib, scrotum, and around left kidney and aorta. He underwent biopsy of the right rib lesion which demonstrated + AFB on smear and histiocytic inflammation, which led to diagnosis of BCGosis, with subsequent cultures positive for Mycobacterium bovis. He was started on multi drug regimen with rifampin, isoniazid and ethambutol. Follow up labs at 4 weeks showed normalization of calcium 8.9 mg/dL, albumin 3.2 g/dL, corrected calcium 9.78 mg/dL, PTH 54 pg/ml and low 1,25 OH vitamin D 17 pg/mL. Calcium and 1,25 OH vitamin D levels were stable at 4 months follow up. Conclusion Intravesical BCG treatment can be associated with systemic reactions in 1- 5% of patients. Granulomas associated with disseminated BCG infection can lead to hypercalcemia due to increased 1-alpha-hydroxylase activity in macrophages, causing elevated 1,25 OH vitamin D levels. Therefore, evaluation of 1,25 OH vitamin D levels is critical to determine the etiology of hypercalcemia. Treatment of underlying BCGosis with anti-tuberculosis treatment is key in management of hypercalcemia along with supportive treatments that may include IV hydration, bisphosphonates and/or glucocorticoids. Presentation: No date and time listed

ODP387 Hemihypertrophy: A Rare Clinical Presentation of Cushing's disease

Abstract Background Hemihypertrophy is a rare clinical presentation of Cushing's disease. It has been described in three newborns with massive enlargement of adrenal glands in presence of other congenital abnormalities and in a 17-year-old female with pituitary adenoma with a genetic diagnosis of Beckwith Weidman syndrome. We describe a case of Cushing's disease with lower extremity hemihypertrophy in the absence of features suggestive of an underlying syndrome. 1,2 Clinical Case: A 12-year-old male with no significant past medical history presented with poor growth and rapid weight gain. In addition, he had hemihypertrophy of left lower extremity interfering with his physical activity. Physical exam showed Tanner Stage 1 for pubic hair and testicular volume of 4 ml bilaterally, with no signs of hirsutism, bruising or purplish striae. Initial work up showed normal thyroid hormone and growth factor levels. Midnight salivary cortisol levels were 238 ng/dl and 51 ng/dl respectively (range &amp;lt;100 ng/dl). One mg dexamethasone suppression test showed suppressed cortisol level of 1 mcg/dl. At the subsequent visit seven months later, he had gained 13.8 kg and grown 0.9 cm in height. Physical exam showed facial plethora and buffalo hump, which had not been present at the initial visit. Left and right leg circumference above the knee were 22 inches and 20 inches respectively. Repeat midnight cortisol levels on two separate occasions were 251 ng/dl and 441 ng/dl respectively. Repeat 1 mg dexamethasone suppression test showed suppressed cortisol levels of 1.2 mcg/dl. Because of clinical picture consistent with Cushing syndrome and elevated salivary cortisol levels, 24-hour urine cortisol levels were ordered that were 145 mcg and 276 mcg/24h respectively (range 1-45 mcg/24hours). ACTH was elevated at 65 pg/ml. CT scan of abdomen and pelvis was normal. Left leg ultrasound was normal. MRI of brain showed a 4 mm hypoenhancing lesion in the pituitary gland to the left of midline. A peripheral DDAVP stimulation test showed elevated ACTH and cortisol levels suggestive of pituitary origin. MRI of legs showed asymmetric fat deposition causing hemihypertrophy. Patient underwent transsphenoidal resection of pituitary adenoma with postoperative remission (postop cortisol nadir &amp;lt;1 mcg/dl). At follow up visit after surgery, patient had lost 0.2 kg, buffalo hump had disappeared, and left leg circumference had slightly improved. Genetic testing ispending. Conclusion This case demonstrates that hemihypertrophy can be a presenting symptom of Cushing's disease.

DIAGNOSING A PROBABLE CASE OF THYROID HORMONE RESISTANCE IN A RESOURCE-POOR SETTING

Resistance to Thyroid Hormone (RTH) is a rare inherited condition usually caused by mutations of the thyroid hormone receptor beta (THRB), thyroid hormone cell membrane transporters, or thyroid hormone metabolism which can present as asymptomatic, hypothyroidism, or hyperthyroidism. The objective is to report a probable case of RTH presenting with hypothyroidism and to demonstrate the resilience in the diagnosis of endocrine disorders in resource-poor settings. A 23-year old University undergraduate presented with clinical features of hypothyroidism but elevated thyroid hormones and thyroid stimulating hormone (TSH): free T4=38 [normal range 10-24] pmol/L, free T3=11 [normal range 3-8] pmol/L, TSH=3.8 [normal range 0.5-5.0] mU/L; and normal brain MRI. A working diagnosis of RTH was made. Though there was no facility to test for THRB gene mutation, the positive family history of a similar pattern of thyroid function tests, made for a probable diagnosis of RTH, and she was empirically placed on a gradually increased dose of levothyroxine from 50 µg till resolution of symptoms was achieved and maintained 6 months later at 600 µg daily. At 10 months follow-up, the patient felt well with the resolution of symptoms and improved academic performance despite elevated thyroid hormones and unsuppressed TSH. The diagnosis of RTH requires a high index of suspicion, to enable early diagnosis, and prevent unnecessary invasive treatments. The treatment target should be the resolution of symptoms and signs and not normalization of thyroid hormone levels. This report also underscores the resilience that can be adopted in diagnosing and treating endocrine cases in resource-poor settings.

Biochemical and Bioinformatic Characterization of Patients with a Sodium Taurocholate Cotransporting Polypeptide Mutation

Background: SLC10A1 codes for the sodium taurocholate cotransporting polypeptide (NTCP). The SLC10A1S267F mutation is associated with loss of function of bile acid (BA) uptake and defined as a new type of hypercholanemia. This kind of hypercholanemia is characterized by high levels of serum BA. However, limited studies have been conducted on this topic. Objectives: This study aimed to describe the biochemical and bioinformatic characterization of patients with an SLC10A1S267F mutation, as well as to dissect pathogenesis in hypercholanemia. Methods: In this study, a total of 12 individuals (including 5 homozygous, 3 heterozygous, and 4 wild-type individuals) were recruited. Whole-genome sequencing (WGS) and Sanger sequencing were used to confirm the genotype. Tests of liver function, renal function, and serum lipid level, in addition to routine blood tests, were performed to evaluate the clinical consequences of patients with an SLC10A1S267F mutation. The ClinVar website and protein prediction tools were used to analyze other cholesterol and BAs related gene mutations in SLC10A1S267F patients, as well as to evaluate their possible effects on serum BA levels of patients. Results: All SLC10A1S267F homozygous patients displayed high levels of BAs. Liver and renal functions were generally normal. According to previous reports, homozygous patients are prone to vitamin D deficiency and deviated blood lipids. However, all homozygous individuals had normal levels of blood lipids, thyroid hormones, and vitamin D (25(OH)D). Moreover, except for the SLC10A1S267F mutation, according to the WGS results, multiple gene mutations were found in 5 homozygous and might affect the level of BAs, but the SLC10A1S267F mutation still is the most important reason resulting in a high level of BAs. Conclusions: This study provided a more detailed description of the SLC10A1S267F mutation-induced hypercholanemia, delivering a new idea that there might be some mutations in SLC10A1S267F homozygotes, probably influencing BA metabolism.

A Low Free T3 to Free T4 Ratio Is Associated with Sarcopenia in Euthyroid Patients with Type 2 Diabetes Mellitus

Background This research evaluated the link between normal thyroid hormone levels and sarcopenia in patients with type 2 diabetes mellitus (T2DM). Methods This cross-sectional study enrolled 312 euthyroid patients with T2DM from Qilu Hospital of the Shandong University, China. Body composition, grip strength, and physical performance were assessed as per the 2019 consensus guidelines of the Asian Working Group for Sarcopenia. Binary logistic regression was used to examine the correlation between thyroid hormone levels and sarcopenia and its components. Results The prevalence of sarcopenia was 26.9%. Following adjustments for potential confounders, a high-normal serum free triiodothyronine (FT3) level (odds ratio (OR) = 0.522, 95% confidence interval (CI): 0.304–0.895, P = 0.018), a low-normal serum free thyroxine (FT4) level (OR = 1.126, 95% CI: 1.009–1.258, P = 0.034), and a heightened FT3/FT4 ratio (OR = 0.923, 95% CI: 0.879–0.969, P = 0.001) were linked to a low prevalence of sarcopenia. Considering the components of sarcopenia, FT3 concentration was positively associated with muscle strength (OR = 0.525, 95% CI: 0.305–0.902, P = 0.020) and physical performance (OR = 0.443, 95% CI: 0.259–0.758, P = 0.003), while FT4 concentration was negatively linked to muscle mass (OR = 1.114, 95% CI: 1.009–1.232, P = 0.036). The FT3/FT4 ratio was positively linked to muscle mass (OR = 0.943, 95% CI: 0.905–0.981, P = 0.006), muscle strength (OR = 0.945, 95% CI: 0.901–0.992, P = 0.021), and physical performance (OR = 0.934, 95% CI: 0.894–0.975, P = 0.002). Nevertheless, thyroid-stimulating hormone concentration was not associated with sarcopenia. Conclusion A high FT3/FT4 ratio was significantly linked to a lowered risk of sarcopenia in euthyroid patients with T2DM.

Follow-Up of Thyroid Function in Children With Neonatal Hyperthyroidism.

IntroductionNeonatal hyperthyroidism mainly occurring in the children born to mothers with Graves’ disease (GD). The influence of maternal GD on the newborn’s thyroid function includes not only hyperthyroidism, but also various forms of hypothyroidism. Maternally transferred thyrotropin receptor antibodies (TRAb), the antithyroid drug (ATD) administration during pregnancy and previous definitive treatment of GD (radioactive iodine therapy or thyroidectomy) in the mother impact the function of the fetal/neonatal thyroid. Some newborns born to mothers with GD may present central hypothyroidism (CeH) due to impaired regulation of the fetal hypothalamic-pituitary-thyroid axis. The aim of this study was to evaluate different types of thyroid dysfunction in babies with neonatal hyperthyroidism.Materials and MethodsMedical records of 14 infants with neonatal hyperthyroidism (13 born to mothers with GD, and one born to mother with Hashimoto thyroiditis) were analyzed.ResultsTransient hyperthyroidism was the main thyroid dysfunction in our study group. Overt hyperthyroidism with highly increased TRAb levels (mean 13.0 ± 7.0 IU/L) was diagnosed in 6 (43%) neonates. Another 6 (43%) babies presented hyperthyroidism with slightly increased fT4 and/or fT3 levels and TSH levels in the lower limit of the normal range coinciding with positive TRAb levels (mean 3.8 ± 1.6 IU/L). Normal thyroid hormone levels with TSH levels below the lower limit of the range were observed in 2 (14%) neonates. Four babies in the study group (28.5%) required further levothyroxine (L-T4) supplementation due to CeH or, in one case, due to primary hypothyroidism.ConclusionOur study highlights the need for prolonged monitoring of thyroid function in children born to mothers with GD. Diagnosis of CeH could be delayed due to its masking by transient hyperthyroidism. Prolonged thyroid-stimulating hormone suppression after TRAb elimination should be considered as a signal announcing CeH.

Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome.

Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites’ composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation.

Subclinical hypothyroidism

Subclinical hypothyroidism is usually a laboratory diagnosis without significant symptoms and is defined by an elevated thyroid-stimulating hormone (thyrotropin, TSH) with normal thyroid hormone levels. On laboratory checks after two to three months, spontaneous normalization is found in 50 % of all cases in the sense of a transient elevation.With persistently elevated TSH levels, subclinical hypothyroidism is associated with evidence of thyroid-specific antibodies in the sense of autoimmune thyroiditis. Physiologically higher TSH levels are found in old age. It can therefore be assumed that the diagnosis of subclinical hypothyroidism is made and treated too frequently in older people over 70years of age.Studies have so far failed to show a positive effect of substitution therapy of subclinical hypothyroidism, especially in elderly patients. On the other hand, there is a not inconsiderable risk of overtreatment with the development of subclinical hyperthyroidism. Its negative consequences in the form of atrial fibrillation and osteoporosis impair the quality and duration of life. Therefore, the indication for substitution therapy of subclinical hypothyroidism should be made with caution.One group in which diagnosis and therapy require special sensitivity is pregnant women. Here, two individuals, mother and child, must be treated. Varying target values and dosages in relation to the gestational age must be taken into account.

Autoimmune Thyroid Disorders in Autoimmune Addison Disease.

ContextAutoimmune thyroid disease is the most common endocrine comorbidity in autoimmune Addison disease (AAD), but detailed investigations of prevalence and clinical course are lacking.ObjectiveThis work aimed to provide comprehensive epidemiological and clinical data on autoimmune thyroid disorders in AAD.MethodsA nationwide registry-based study including 442 patients with AAD and autoimmune thyroid disease were identified through the Norwegian National Registry of Autoimmune Diseases.ResultsOf 912 registered AAD patients, 442 (48%) were diagnosed with autoimmune thyroid disease. A total of 380 (42%) had autoimmune hypothyroidism. Of the 203 with available thyroid function tests at time of diagnosis, 20% had overt hypothyroidism, 73% had subclinical hypothyroidism, and 7% had thyroid levels in the normal range. Negative thyroid peroxidase antibodies was found in 32%. Ninety-eight percent were treated with levothyroxine, 5% with combination therapy with liothyronine or thyroid extracts, and 1% were observed without treatment. Seventy-eight patients (9%) were diagnosed with Graves disease (GD), of whom 16 (21%) were diagnosed with autoimmune hypothyroidism either before onset or after remission of GD. At the end of follow-up, 33% had normal thyroid hormone levels without antithyroid-drugs or levothyroxine treatment. The remaining had either active disease (5%), had undergone ablative treatment (41%), or had developed autoimmune hypothyroidism (21%).ConclusionThe true prevalence of hypothyroidism in AAD is lower than reported in the current literature. Careful consideration of the indication to start thyroxin therapy is warranted. Long-term remission rates in GD patients with AAD are comparable to recent reports on long-term follow-up of patients without AAD.

Hashimoto's Encephalopathy Masquerading as Rapidly Progressive Dementia and Extrapyramidal Failure.

Hashimoto's encephalopathy is a rare immune-mediated disorder characterized by subacute encephalopathy with elevated thyroid antibodies. Hashimoto's encephalopathy is also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis. We report a rare presentation of Hashimoto's encephalopathy presenting with acute neuropsychiatric disturbances, rapidly progressive dementia, seizures, and extrapyramidal failure. Neuroimaging revealed multifocal vasculitides of major cerebral vessels that support the autoimmune vasculitic theory as the underlying pathogenesis for Hashimoto's encephalopathy. Unfortunately, permanent irreversible cerebral damage has already ensued before her presentation to our center, which rendered steroid therapy ineffective. Serological testing for Hashimoto's thyroiditis must be in the investigation of all rapidly progressive dementias as early diagnosis and timely management of autoimmune thyroiditis may salvage sizable and eloquent cerebral tissues. The rarity of the condition should not preclude the investigation of Hashimoto's disease even in the presence of normal levels of thyroid hormones. Delayed diagnosis may result in irreversibly catastrophic encephalopathy in patients who once presented with potentially curable dementia.

ОСОБЕННОСТИ ЛИПИДЕМИИ И АТЕРОСКЛЕРОТИЧЕСКОГО ПОРАЖЕНИЯ КОРОНАРНОГО РУСЛА У ЛИЦ С ОСТРЫМ КОРОНАРНЫМ СИНДРОМОМ И СУБКЛИНИЧЕСКИМ ГИПОТИРЕОЗОМ

Objective: To assess the derangements in lipid metabolism and the severity of atherosclerotic disease of the coronary arteries in patients with the acute coronary syndrome (ACS) and subclinical hypothyroidism (SHT). Methods: 146 medical records of inpatients of working age with newly developed ACS and various thyroid hormonal statuses were analysed. The lipid profile, high-sensitivity C-reactive protein (hs-CRP), thyroid-stimulating hormone (TSH), and free thyroid hormones (free thyroxine, FT4, and free triiodothyronine, FT3) levels were investigated. Coronary angiography results were used to assess coronary atherosclerotic plaque burden. The study group comprised 67 patients with ACS and SHT (TSH level &gt;4.0 mIU/l with normal thyroid hormone levels), and the control group included 79 ACS patients without thyroid hormonal abnormalities. The groups were matched for the presence of unhealthy habits, gender, age, and severity of arterial hypertension. Before admission to the hospital, patients did not receive preventive therapy for coronary artery disease (CAD) or hormone replacement therapy. Results: In SHT patients, in comparison with the group of patients with normal thyroid function, the proportion of individuals with type IIa hyperlipidemia was higher – 82.0% (n=55) and 46.8% (n=37), respectively (χ2=19.33; p&lt;0.001). A medium strength direct correlation was established between laboratory confirmed SHT and atherogenic dyslipidemia (r=0.62; p&lt;0.01), an increase in the level of hs-CRP (r=0.74; p&lt;0.01), and multivessel CAD (r=0.58; p&lt;0.05). Conclusion: In patients with CHT, the proportion of individuals with multivessel coronary artery stenosis is higher, and CAD occurs in the presence of hs-CRP and atherogenic dyslipidemia. Keywords: Acute coronary syndrome, coronary artery disease, atherosclerosis, hyperlipidemia, subclinical hypothyroidism, thyroid gland.

Autoimmune thyroid disease and thyroid function test fluctuations in patients with resistance to thyroid hormone.

Resistance to thyroid hormone beta (RTHβ) is an inherited syndrome caused by mutations in the thyroid hormone receptor β (THRB) gene. Patients with RTHβ typically have elevated thyroid hormone levels with non-suppressed serum thyroid-stimulating hormone (TSH). We aimed to elucidate the clinical, laboratory, and imaging findings of RTHβ patients and further to explore their association with THRB gene mutations. We retrospectively reviewed the clinical charts and compared the clinical findings of 68 RTHβ patients (45 probands and 23 relatives) and 30 unaffected relatives in Kuma Hospital. Genetic testing revealed 35 heterozygous THRB gene mutations. Among all RTHβ patients, autoimmune thyroid disease (AITD) was detected in 42.1% of men and 40.9% of women, showing that the prevalence of AITD in affected males was significantly higher than in unaffected relatives (P = 0.019). During the follow-up of 44 patients, 13 patients (29.5%; 8 (42.1%) with AITD and 5 (20%) without AITD) temporarily showed thyroid function test results inconsistent with RTHβ. Two patients with the R383H mutation, which has little dominant-negative effect, temporarily showed normal thyroid hormone and TSH levels without AITD. The frequency of AITD in male RTHβ patients was significantly higher compared to unaffected relatives. More than 20% of RTHβ patients temporarily showed laboratory findings atypical of RTHβ during their follow-up, and patients with AITD and specific THRB mutations were prone to display such findings. Therefore, genetic testing should be performed even for patients with fluctuations in thyroid function test results to avoid misdiagnosis and inappropriate treatment.

Reduced pituitary size in subjects with mutations in the THRB gene and thyroid hormone resistance.

BackgroundThyroid hormone action is mediated by two forms of thyroid hormone receptors (α, β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify the effects of mutant TRβ on pituitary size.MethodsHigh-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist).ResultsPatients with mutant TRβ (resistance to thyroid hormone β, RTHβ) showed elevated free tri-iodothyronine/thyroxine levels with normal thyroid-stimulating hormone levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35) = 7.05, P = 0.012, partial η2 = 0.17).ConclusionRTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.

Abstract 13197: Increased Cardiac and All-Cause Mortality After Percutaneous Coronary Intervention in Subclinical Hypothyroidism: A Meta-Analysis

Background: Subclinical hypothyroidism (elevated TSH with normal thyroid hormone levels), is associated with an increased risk of cardiovascular diseases like atherosclerosis and coronary artery disease. However, its impact on long-term outcomes after percutaneous coronary intervention (PCI) remains understudied. Methods: PubMed, EMBASE, and Web of Science databases were screened through June 2021 for studies reporting long-term PCI outcomes in patients with subclinical hypothyroid state vs. Euthyroid state. Random effects models were used for the meta-analysis. I2 statistics were used to interpret heterogeneity with I 2 &gt;75% indicating substantial inter-study variation. A sensitivity analysis was performed using the leave one out method. A p-value &lt;0.05 was considered statistically significant. Results: A total of 6 studies including 11,664 patients who had undergone PCI were identified with a median follow-up period of 3.75 years. There were 987 patients identified with subclinical hypothyroidism and the mean age of the cohort was 67.15 ± 9.9 years. It consisted of 48% males, the most common comorbidities were hypertension (70%) followed by diabetes mellitus (33%). In-hospital outcomes were reported only in one study while long-term outcomes were reported in all 6 studies. Pooled analysis for long-term adverse events showed that subclinical hypothyroidism was associated with increased all-cause (OR 1.78, 95%CI: 1.16-2.72, p&lt;0.01, I 2 =50.67%) and cardiac mortality (OR 1.41, 95%CI: 1.09=1.81, p&lt;0.01, I 2 =0%) over long-term follow-up following PCI Conclusions: Subclinical hypothyroidism at times remains undiagnosed or underdiagnosed, however, it predicts significantly higher all-cause and cardiac mortality in the long term following PCI compared to controls. Therefore, it is recommended to regularly screen and manage high-risk patients undergoing PCI with underlying subclinical hypothyroidism.

Thyrotropin, Hyperthyroidism, and Bone Mass.

Thyrotropin (TSH), traditionally seen as a pituitary hormone that regulates thyroid glands, has additional roles in physiology including skeletal remodeling. Population-based observations in people with euthyroidism or subclinical hyperthyroidism indicated a negative association between bone mass and low-normal TSH. The findings of correlative studies were supported by small intervention trials using recombinant human TSH (rhTSH) injection, and genetic and case-based evidence. Genetically modified mouse models, which disrupt the reciprocal relationship between TSH and thyroid hormone, have allowed us to examine an independent role of TSH. Since the first description of osteoporotic phenotype in haploinsufficient Tshr +/- mice with normal thyroid hormone levels, the antiosteoclastic effect of TSH has been documented in both in vitro and in vivo studies. Further studies showed that increased osteoclastogenesis in Tshr-deficient mice was mediated by tumor necrosis factor α. Low TSH not only increased osteoclastogenesis, but also decreased osteoblastogenesis in bone marrow-derived primary osteoblast cultures. However, later in vivo studies using small and intermittent doses of rhTSH showed a proanabolic effect, which suggests that its action might be dose and frequency dependent. TSHR was shown to interact with insulin-like growth factor 1 receptor, and vascular endothelial growth factor and Wnt pathway might play a role in TSH's effect on osteoblasts. The expression and direct skeletal effect of a biologically active splice variant of the TSHβ subunit (TSHβv) in bone marrow-derived macrophage and other immune cells suggest a local skeletal effect of TSHR. Further studies of how locally secreted TSHβv and systemic TSHβ interact in skeletal remodeling through the endocrine, immune, and skeletal systems will help us better understand the hyperthyroidism-induced bone disease.

Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape.

Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

Associations of Thyroid Hormone Levels and Macrovascular Complications in Euthyroid Type 2 Diabetic Patients.

PurposeThe purpose of this study is to evaluate whether thyroid hormone in euthyroid patients with type 2 diabetes mellitus (T2DM) is associated with macrovascular complications.Patients and MethodsThe authors examined 311 patients enrolled from February 2019 to December 2019 in Tianjin Medical University Chu Hsien-I Memorial Hospital. A medical record review enabled the collection of demographic and anthropometric information. We classified the patients into two groups based on the echocardiography and vascular ultrasonography results, namely, non-macrovascular complications (n=131) group and macrovascular complications (n=180) group. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for potential confounders, the prevalence of macrovascular complications was determined using multivariate logistic regression.ResultsA significant association was observed for diabetic macrovascular complications with normal free triiodothyronine (FT3) (OR=0.534, 95% CI 0.358–0.796, p = 0.002) and free thyroxine (FT4) (OR= 0.844, 95% CI 0.760–0.937, p = 0.001). Nevertheless, there was no evidence of any association between thyroid-stimulating hormone (TSH) and the development of diabetic macrovascular complications. When stratified by the body mass index (BMI), a similar relationship existed with the overall results. The positive association remained in restricted analyses involving only patients with HbA1c abnormalities.ConclusionOverweight or obese T2DM patients are at high risk due to the implicit association between low but clinically normal thyroid hormone levels and elevated risk of macrovascular complications. However, there were no statistically significant associations between TSH and diabetic macrovascular complications.

Bone Microarchitectural Changes in Hyperthyroid Women Compared to a Normal Canadian Cohort

Thyroid hormones play a critical role in bone physiology during childhood, but also impacts adult bone metabolism. Hyperthyroidism promotes accelerated bone turnover and bone remodelling which is associated with net loss of bone mineral density over time (BMD) and these changes have been quantitated using the gold standard of measuring BMD, Dual Energy X-ray Absorptiometry (DEXA). Ordinarily, biochemical thyroid hormone normalization restores BMD towards normal, yet an increased risk of fractures remains lifelong. DEXA, therefore, cannot explain the underlying etiology for fracture risk which may be due to undetected changes in bone microarchitecture. Our primary objective was to utilize an investigational 3-dimensional bone imaging technology, High Resolution peripheral Quantitative Tomography (HR-pQCT), to study bone microarchitecture in actively hyperthyroid women to determine if there are changes in cortical and trabecular bone microarchitecture from that of age-matched controls. A subset of women were rescanned using HR-pCT after thyroid hormones had been normalized for at least 6 months to determine if there were cortical/trabecular architectural changes that reversed towards normal in these individual cases.We enrolled 20 hyperthyroid women (age 20–76) for this pilot study who had persistent TSH suppression for >3 months (TSH< 0.5, normal range: 0.5–4.49 mU/L) without secondary causes for bone loss. Their etiology was divided amongst TSH suppression for thyroid carcinoma, Grave’s disease and iatrogenic hyperthyroidism. HR-pQCT scans of the radius were compared to age-matched scans of normal females, available from the robust Canadian Multicentre Osteoporosis Study (CaMOS) control cohort. Four participants were re-scanned after 6 months of TSH normalization to assess reversibility. The observed data showed statistically significant differences in key parameters of bone microarchitecture in hyperthyroidism, independent of etiology. We observed decreased cortical thickness and increased failure load as statistically different from age-matched controls. Increases in cortical bone porosity and decreases in volumetric bone density (cortical, trabecular and total) were notable but did not reach significance in this small study. Repeat scans following normalization of thyroid hormone levels revealed consistent (partial, nonsignificant) normalization of multiple bone microarchitecture elements including increased trabecular number/thickness, and decreased cortical porosity. These findings suggest that there are changes in both cortical and trabecular bone during active hyperthyroidism that may contribute to increased lifelong fracture risk.