Family History Of Hypothyroidism Research Articles

Cutaneous manifestations of hypothyroidism: An observational study in a tertiary care center of Eastern India

Cutaneous manifestations of hypothyroidism: An observational study in a tertiary care center of Eastern India

THU237 A Case Of Primary Hypothyroidism, Dysglycemia And Epilepsy With PAX8 And SETD1A Mutation

Abstract Disclosure: S.K. Singh: None. KEYWORDS: PAX8, SETD1A, DYSGLYCEMIA INTRODUCTION: Hypothyroidism is associated with dysglycemia linked with insulin resistance and shared common genetic determinants.PAX 8 gene regulates the development of thyroid gland as well as the expression of TG,TPO and NIS genes.It impacts glucose homeostasis by favoring beta-cell survival and through thyroid hormones.Epilepsy in hypothyroid patients can be idiopathic or due to Hashimoto’s Encephalopathy (HE). Thyroid hormones can impact epileptogenesis through mitochondrial dysfunction, oxidative-stress and GABAergic transmission. THE INDEX PATIENT: A 13 year old female(weight and height age 1.5 years below her chronological age by Indian growth chart and a further lag of 18 months and 6 months, respectively by CDC chart)was diagnosed as a case of thyroprivic hypothyroidism with TSH - 100 mIU/L and positive anti-TPO antibody. She was euthyroid on 112 ug/d L-T4.She is on anticonvulsant since 12 years of age for tonic-clonic epilepsy. The MRI of brain showed focal gliosis with few small encephalomalacic streaks in right occipital lobe. On evaluation at 12.5 years of age, her fasting plasma glucose was 80 mg/dl and her HbA1c was 4.8% but 2-h post glucose was 233 mg/dl with another value of 270 mg/dl. Her father has T2DM and Hypothyroidism. Her mother is Hypothyroid. Her genetic study showed SETDIA and PAX8(-) mutations. DISCUSSION: PAX8 regulates development of thyroid gland and biosynthesis of thyroid hormones. It can impact glucose homeostasis by enhancing beta-cell survival by inhibiting apoptosis, immunomodulation, maintaining local anti-inflammatory milieu in pancreas, ensuring systemic levels of thyroid hormone to stimulate insulin secretion and protect beta-cells from environmental stressors.PAX8 mutation in a family has been shown to be associated with a spectrum of disorders encompassing Gestational Thyroid Dysfunction(GTD),Gestational Diabetes Mellitus(GDM) and T2DM.[1] Although mutation analysis was done only in the index patient, Hypothyroidism and Dysglycemia (post- glucose>200 mg/dl)in the patient and family history of Hypothyroidism and T2DM could be linked with PAX8 mutation.SETD1A mutation has been linked with early-onset epilepsy with or without developmental delay. The mutation study can aid in deciding appropriate therapy including steroids for HE. CONCLUSION: This case highlights the significance of evaluation for PAX8 mutation in hypothyroid patients, even if anti-TPO positive, particularly when there is family history of thyroid dysfunction, GDM, T2DM. It also underlies the importance of SETD1A mutation analysis in hypothyroid patients with epilepsy. Presentation: Thursday, June 15, 2023

The Relationship Between Maternal Hypothyroidism and the Incidence of Congenital Hypothyroidism in Infants: A Cross-Sectional Study

Background: Congenital hypothyroidism (CH) can influence neonates’ neurodevelopment. There are controversies on the cause of infantile hypothyroidism and its relationship with maternal hypothyroidism. Objectives: This study aimed to investigate the relationship between maternal hypothyroidism and the incidence of CH. Methods: This cross-sectional study was conducted on 712 newborns with hypothyroidism born in Fars province, Iran, between 2018 and 2020, identified through the national screening program for genetic, metabolic, and endocrine congenital diseases recruited by the census sampling method. The information on infants’ files was recorded in a researcher-made checklist. Descriptive data were reported by mean ± SD and No. (%). The independent t-test, chi-square test, Pearson correlation, and Spearman’s rank correlation coefficient were used to evaluate relationships between variables. Results: Of 179,448 infants screened, 712 (4 of 1,000 live births) had CH with a mean thyroid stimulating hormone (TSH) level of 22.34+24.8 mlU/L. Of these, 252 infants (35.4%) had a family history of hypothyroidism in the mother (OR = 4.951, P < 0.001). There was a significant relationship between CH and maternal hypothyroidism. Moreover, there was a significant difference in the mean TSH level between hypothyroid infants born to mothers with a history of hypothyroidism (19.10 ± 21.30 mlU/L) and those who had healthy mothers (24.23 ± 26.44 mlU/L, P = 0.027). The prevalence of CH in 2018, 2019, and 2020 were reported to be 0.34%, 0.4%, and 0.45%, respectively. Conclusions: Our results showed a significant relationship between maternal hypothyroidism and CH. Considering the importance of the prompt diagnosis of CH, especially in high-risk groups such as infants of hypothyroid mothers, it is recommended to conduct more studies to design more precise guidelines to screen infants who are at risk of CH.

Frequency of congenital hypothyroidism in healthy newborns.

Objective: To determine the frequency of congenital hypothyroidism (CH) in healthy newborns. Study Design: Cross-sectional study. Setting: Department of Neonatology, Children Hospital & Institute of Child Health Multan. Period: July 2020 to January 2021. Material & Methods: Neonates of both genders between 48 hours of life to 28 days of age delivered after 37-weeks of gestation were analyzed. All the neonates underwent blood sample testing for congenital hypothyroidism (T4 and TSH). The CH was described as neonates having T4 levels < 0.85 ng/dl and TSH > 40 mIU/L. Frequency of CH (yes/no) was noted. Results: Of these 146 study cases, 77 (52.7 %) were male participants while 69 (47.3 %) were female. Mean gestational age of our study cases was 38.12 ± 0.78 weeks. Of these 146 study cases, 40 (27.4 %) belonged to rural areas and 106 (72.6 %) belonged to urban areas. Poor socioeconomic status was noted in 46 (31.5%) while 100 (68.5%) were from middle income families. Of these 146 study cases, 109 (74.7%) were born vaginally while 37 (25.3%) were born through cesarean section. Family history of hypothyroidism was positive in 15 (10.3) cases. Mean body mass index of their mothers was 24.21 ± 2.33 kg/m2 and maternal obesity was present in 22 (15.1 %) in our study cases. Congenital hypothyroidism was noted in 12 (8.2%). Conclusion: High frequency (8.2%) of congenital hypothyroidism was noted in healthy newborn babies. Congenital hypothyroidism was significantly associated with mode of delivery and family history of hypothyroidism.

Clinical features and outcomes of 31 children with congenital hypothyroidism missed by neonatal screening.

To investigate the clinical features and outcomes of children with congenital hypothyroidism (CH) missed by neonatal screening. The clinical and laboratory date of 31 children with CH missed by neonatal screening from February 2015 to February 2022 in Guangzhou Women and Children's Medical Center were retrospectively analyzed. Whole-exome high-throughput sequencing analysis was performed in 17 patients. Among the 31 patients, 19 cases (61.3%) were preterm, 12 cases (38.7%) were term neonates. The median value of gestation age was 36 (26-40) weeks, birth weight was 2.35 (0.75-3.70) kg, diagnosed age was 20 d (7 d-4 years), dry blood spot thyrotropin was 4.18 (0.34-8.97) mU/L. Nine cases (29.0%) were same-sex twins and 4 cases (12.9%) had a family history of hypothyroidism. The initial clinical symptoms were growth retardation in 11 cases (35.5%), prolonged jaundice in 7 cases (22.6%), short stature, abdominal distension, fetal edema and goiter in 1 case (3.2%), respectively. Genetic analysis of the 17 children showed that DUOX2 gene mutations were detected in 10 cases (6 cases with biallelic mutations and 4 cases with monoallelic mutations), of whom 3 had a family history of hypothyroidism. A total of 22 patients were reevaluated at the age of 2-3 years, of whom 17 cases (77.3%) were transient CH and 5 cases (22.7%) were permanent CH. Among the 10 cases with DUOX2 gene mutations, 6 cases were transient CH, 1 case was permanent CH, and 3 cases (< 3 years old) were still under treatment with L-thyroxine. False negative results on neonatal screening for CH often occurs in preterm birth, low birth weight, same-sex twins, family history of hypothyroidism, and DUOX2 defects are the common molecular pathogenesis, most of whom are transient CH. Thyroid function should be evaluated in time for children with unexplained slow growth and delayed jaundice regression.

Severe primary hypothyroidism in an apparently asymptomatic 19-year-old woman: a case report

BackgroundHypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism.Case presentationWe report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient’s insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment.ConclusionThere is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.

Produžena i nelečena hipotireoza kao jedan od mogućih uzroka akutne psihotične epizode

Psychosis is a set of symptoms that lead to contact disorders or even cessation of contact with reality. It can be in the form of disorders of perception, emotions, thoughts, and behavior. Psychosis has many causes, and one of them is hypothyroidism. Thyroxin is important for the global function of brain activity, cholinergic activity in the frontal cortex and hippocampus increases significantly in its presence. The diagnosis of psychotic episodes is made on the basis of autoanamnesis and heteroanamnesis, as well as psychiatric examination. The presence of: positive syndrome, disorganization and negative syndrome. After the diagnosis of a psychotic disorder, antipsychotics are included in the therapy, and upon arrival, the findings that verify hypothyroidism, include thyroxin in the therapy. The therapeutic response is achieved after a few days or a week. In patients with an acute psychosis, and especially in those with a positive personal and family history of hypothyroidism, one should think in the direction of an unrecognized endocrine disease.

Trend of Congenital Hypothyroidism Incidence and its Affecting Factors in Shahr-e-Kord, Western Iran

Congenital hypothyroidism is one of the most common endocrine disrupters and metabolism, and is one of the most important preventable causes of physical and mental disabilities. This was a case-control study, in which 54468 infants were screened from 2006 to 2014 in Shahre-Kord, western Iran. To describe the data, central and dispersion indices such as mean and standard deviation was used. For modeling, logistic regression was used. All the tests were performed at the significant level of 5%. Overall, 111 cases were diagnosed with hypothyroidism, which made the prevalence value equal to 2 cases per 1000 births. The prevalence in females and males was 1.9 and 2.2 per 1,000 birth, respectively. The odds ratio for this disorder was 4.47(2.42-9.28) for the neonates with a family history of hypothyroidism and 1.72(1.05-2.82) for those born through cesarean. The incidence of this disorder is similar in males and females, and the incidence of this disease in people with a family history is far more than others.

Congenital hypothyroidism: a five-year retrospective study at Children's University Hospital, Damascus, Syria.

Background: Congenital hypothyroidism (CH) is a treatable thyroid hormone deficiency that causes severe mental retardation and growth deficiency if not detected and treated early. The treatment of CH is simple, inexpensive, and effective. With early detection and treatment, infants usually develop normally without mental retardation and become productive members of society. In Syria, a screening program is not available, and there is no published information about the actual incidence of CH. However, an unpublished pilot study supported by the International Atomic Energy Agency showed that the incidence of CH in Syria is more than the global incidence, indicating the importance of the application of a CH screening program in Syria. Objectives: The present study aimed to collect baseline information about CH in Syria to estimate the potential need of a screening program. Materials and methods: This retrospective study was performed at Children's University Hospital, Damascus. The study included the medical records of patients who had CH as the final diagnosis between 2008 and 2012. Some patients were diagnosed elsewhere and were then admitted to the hospital within the same period. Results: In this study, 70 cases registered as CH, 67 of them had confirmed, 40 (57.1 %) were male and 30 (42.9%) were female. Among the patients, (51.4%, n = 36) involved parental consanguinity and 6 had a family history of hypothyroidism. Additionally, 74.3% were not diagnosed during the first month of life. The signs and symptoms most commonly detected were cretinoid face (60%), pallor (44.3%), delayed neuropsychomotor development (37.1%), growth failure (36.7%), jaundice (35.7%), and hypotonia (35.7%). Conclusion: A CH screening program is necessary in Syria owing to the low specificity of the signs and symptoms of CH, which can lead to delayed diagnosis, and the presence of asymptomatic cases (subclinical hypothyroidism).

Pityriasis rubra pilaris: a rare inflammatory dermatosis

An 18-year-old Caucasian woman presented with a 2-week history of a pruritic rash commencing on the face and spreading distally to the trunk and limbs. There were no associated systemic...

Frequecy of hypothyroidism In multi-transfused thalassemic patients in AL- Diwanyia Maternity ??children Hospital

Back ground: hypothyroidism in thalassemic children is not uncommon problem ? and need special attention and frequent patient monitoring.&#x0D; Objective: to establish the frequency of hypothyrodism among multitransfused&#x0D; thalassemic patients depending on clinical and laboratory investigations.&#x0D; Methods: A cross sectional study of thyroid function ,T3,T4, and TSH, was carried out in 120 transfusion-dependent thalassemia and sickle cell anemia patients attended the thalassemic Center in AL-Diwanyia Maternity and Children.Teaching Hospital .The inclusion criteria were 1(the age more than 5 years and 2)receiving frequent blood transfusions at least 6 times per year in the last three years.&#x0D; Result: eight patients have hypothyroidism and had a prevalence of (6.66%). Two patients had low T3 and T4 and elevated TSH with signs and symptoms of hypothyroidism and was already treated with thyroxin ,which consistent with the diagnosis of primary hypothyroidism , and 6 patients had no signs and symptoms of hypothyroidism with normal T3 and T4 but elevated TSH and this was consistent with the diagnosis of subclinical hypothyroidism . No patient of these 8 have family history of hypothyroidism . All affected patients are receiving&#x0D; blood transfusions more than 20 times since the time of diagnosis and all the effected patients have suboptimal iron –chelating therapy as reflected by the high serum ferritin level ( &lt; 1000 ).&#x0D; Conclusion: patient with transfusion dependent hemoglobinpathy need frequent monitoring of their thyroid function at least once yearly to detect early hypothyroidism and start early treatment .

Thyroid function testing in neonates born to women with hypothyroidism.

No extra cases of CH were detected from the thyroid test at 10-14days and this practice should be discontinued due to the robust nature of existing newborn screening programmes. What is Known: • Congenital hypothyroidism(CH) is the commonest preventable cause of childhood intellectual impairment. • Family history of hypothyroidism has been implicated as a risk factor for CH. • CH has formed part of newborn screening since the 1970s. What is New: • There is no research recommending thyroid function testing at 10-14days of life to detect CH in neonates born to mothers with hypothyroidism. • Thyroid function testing at 10-14days of life does not improve diagnostic yield for CH in babies born to mothers with hypothyroidism. • Newborn blood spot remains the mainstay for accurate and timely diagnosis of CH.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 μg/l, and 17·9 % of children showed UI<100 μg/l. The median UI was higher in males (180·8 v. 153·6 μg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Pattern of hypothyroid cases in Bangladeshi People: A pilot study

Aims: The present study was undertaken to explore the pathological basis of hypothyroidism and it relationship to clino-biochemical features of Bangladeshi patients. Material and Methods: A total number of 47 hypothyroid patients with duration less than two years and had no other comorbid disease were consecutively recruited from BIRDEM Out-patient department. Patients having serum FT4 level &lt;9.14 pmol/L and serum TSH &gt;5.01 IU/ml were identified as hypothyroidism. Presence of either anti TG antibody &gt;40 IU/ml or anti TPO antibody &gt; 35 IU/ml or both were defined as autoimmune hypothyroidism. Thyroid gland was examined and classified according to joint criteria of WHO, UNICEF and ICCIDD criteria. Results: Female preponderance was observed in this series though small total number of samples. Familial hypothyroidism was reported in 19% of cases and 8% of patients came from iodine deficient area. Out of 47 cases autoimmune markers were done in 40 and of them 32 (68%) were positive for autoantibodies. Of the positive case 22% were positive for anti TPO antibody and 6% for anti TG antibody; 72% cases both. Drug and radiation were excluded as the cause of hypothyroidism in this series. Family history of hypothyroidism was positive in 22% and 25% autoimmune and non-autoimmune study cases. Of the autoimmune case 44% had age between 30-44 years and among non-autoimmune case 37% were 15-30 years. Eleven of 32 (34%) autoimmune hypothyroid cases presented with irregular menstrual cycle. Out of 47 hypothyroid patients in this study, 36 (77%) had palpable or enlarged thyroid gland. Of the 40 cases autoimmune status evaluated palpable among 25 (78%) autoimmune and 6 (75%) non-autoimmune hypothyroid patients. Conclusions: It is concluded that higher proportion of hypothyroid cases are of antoantibody positive. These subjects have heterogeneous phenotypic presentation. This necessitates that all newly detected hypothyroidism should be screened for autoimmune status with the same importance as given for thyroid hormone level and managed accordingly. DOI: http://dx.doi.org/10.3329/bjms.v12i4.16660 Bangladesh Journal of Medical Science Vol. 12 No. 04 October ’13 Page 405-412

Late Primary Autoimmune Hypothyroidism in a Patient with Postdelivery Autoimmune Hypopituitarism Associated with Antibodies to Growth Hormone and Prolactin-Secreting Cells

Pituitary and thyroid autoimmunity can be triggered by pregnancy. We report the first association of combined growth hormone (GH) and prolactin secretion deficiency due to autoimmune damage to GH- and prolactin-secreting cells in a patient with postdelivery lactation failure, presenting subsequently with primary autoimmune hypothyroidism. A 34-year-old woman presented with lactation failure following the delivery of her first child. She had a family history of hypothyroidism without a history of pituitary dysfunction. Physical examination did not show any abnormal findings. Laboratory investigations showed normal gonadotropin levels after the restoration of normal menstrual cycles following pregnancy, normal basal and stimulated cortisol levels, but an impaired GH response to insulin-induced hypoglycemia, and low basal prolactin and insulin-like growth factor-1 concentrations. Thyroid function was normal when initially investigated three months after delivery, but five months later, marked primary hypothyroidism (thyrotropin levels >100 mIU/L) occurred. Immunological investigation revealed the presence of antipituitary antibodies, identified by double immunofluorescence and targeting GH- and prolactin-secreting cells. Antithyroid antibodies, in the normal range three months postpartum, became significantly elevated when the hypothyroidism appeared. Autoimmune hypophysitis is responsible for selective or multiple pituitary-hormone deficiencies, sometimes involving thyrotropin secretion and causing secondary hypothyroidism, but usually associated with hyperprolactinemia. To our knowledge, this is the first observation of autoimmune hypopituitarism involving deficient growth hormone and prolactin secretion in a patient with lactation failure after delivery, subsequently followed by severe primary autoimmune hypothyroidism, thus falling into an unusual constellation of autoimmune polyendocrine syndrome type 3. Considering the well-known relationship between pregnancy and autoimmunity, an early postdelivery immunological and functional investigation in women presenting with disorders of lactation may be useful to detect potential pituitary and thyroid dysfunction even at a subclinical stage.

Association between Primary Hypothyroidism and Nephrotic Syndrome: A Case Report

A 11–year-old girl was admitted in the Department of Paediatric Nephrology, National Institute of Kidney Diseases and Urology (NIKDU), Sher-E-Bangla Nagar, Dhaka. She was diagnosed as a case of nephrotic syndrome associated with primary hypothyroidism. She had short stature and was malnourished, but had no family history of hypothyroidism or renal diseases. She also had no consanguinity. She was treated with oral steroid and levothyroxin associated with nutritional support. Her condition improved with the treatment. At regular follow up her height and nutritional status was improved. Though hypothyroidism may be associated with nephrotic syndrome, it should be carefully evaluated. DOI: http://dx.doi.org/10.11566/cmoshmcj.v12i2.44 Chatt Maa Shi Hosp Med Coll J 2013; 12(2): 63-65

Moderate alcohol consumption may protect against overt autoimmune hypothyroidism: a population-based case–control study

Alcohol consumption is an important protective risk factor for many autoimmune diseases. We wished to study the association between alcohol consumption and autoimmune hypothyroidism. Population-based, case-control study, 1997-2001, Denmark. Patients with newly diagnosed autoimmune overt hypothyroidism (n=140) were prospectively identified in a population (2 027 208 person-years of observation), and their matched controls with normal thyroid function (n=560) were recruited simultaneously from the same population. Participants gave information on alcohol intake, smoking, previous diseases, education, and family history of hypothyroidism. The association between alcohol intake and development of hypothyroidism was analyzed in conditional regression models. Hypothyroid cases had reported a lower alcohol consumption than controls (median units of alcohol (12 g) per week: 3 vs 5, P=0.002). In a multivariate regression model, alcohol consumption was associated with a reduction in risk for development of overt autoimmune hypothyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1-10 units of alcohol per week were as follows: 0 units/week, 1.98 (1.21-3.33); 11-20 units/week, 0.41 (0.20-0.83); and ≥21 units/week, 0.90 (0.41-2.00). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with type of alcohol consumed (wine vs beer), sex, or region of inhabitancy. Alcohol consumption seems to confer considerable protection against development of overt autoimmune hypothyroidism irrespective of sex and type of alcohol consumed.

Isotretinoin Associated Reversible Hypothyroidism

Isotretinoin (13-cis retinoic acid) has been regarded as an effective drug for the treatment of acne. Its wide range of adverse effects limits its use, however (1). Isotretinoin has been reported to disturb thyroid function, causing both reversible hypoand hyperthyroidism (1–3), but this impression is not conclusive. The patient presented here supports an association between use of oral 13-cis retinoic acids and reversible hypothyroidism. A 25-year-old woman presented to the Endocrinology Clinic of Aga Khan University Hospital in February 2010 with complains of a weight gain of 3 kg, along with dull mood and mennorrhagia for the previous 3–4 months. There was no history of cold intolerance, constipation, excessive sleep, lethargy, or hair loss. There was no family history of hypothyroidism. Drug history revealed that for 6 months she had taken isotretinoin, 20 mg once daily, for the treatment of acne. This had been stopped about 6 weeks before her presentation. There was no history of alcohol consumption or any other drug intake during this period. On examination, her pulse was 86 beats per minute, blood pressure was 130/80 mm Hg, and weight was 50.5 kg. A small diffuse goiter was noted; the remainder of her physical examination was unremarkable. Thyroid function tests done 1 month before visit, approximately 2 weeks after stopping the isotretinoin, showed a serum thyroid-stimulating hormone (TSH) of 78.97 mIU/mL (normal range 0.4–4.2), triiodothyronine of 1.51 nM (normal range 1.3–3.1), and thyroxine of 4.42 mg/dL (normal range 5.0–12.0). As she reported progressive improvement in her symptoms over the previous month, thyroid hormone replacement therapy was not instituted and she was asked to repeat her serum TSH. Her TSH done on the day of visit, that is, 6 weeks after stopping isotretinoin, was 15.03 mIU/mL. There was no history of thyrotoxic phase during the preceding several months that could have suggested the hypothyroid phase of thyroiditis. She was advised to follow-up in 6 weeks. When she presented again in March for another visit, she was symptom free. Her lab work-up on that day, 12 weeks after stopping isotretinoin, showed a serum TSH of 3.33 mIU/mL and antithyroid peroxidase enzyme levels of 3.30 IU/mL (<12 IU/mL). She was advised to follow-up in case of recurrence of symptoms and have her serum TSH repeated after 6 months. The effects of vitamin A derivatives on thyroid function have been a topic of interest for a number of years. Bexarotene, a compound closely related to isotretinoin, causes hypothyroidism both by central mechanism and by increasing the peripheral degradation of thyroid hormones by a nondeiodinase mediated pathway (4). In the study conducted by Marsden et al. (2), seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 weeks. Their levels of serum triiodothyronine and thyroxine were significantly lower after treatment, but the response to thyrotropin releasing hormone (TRH) stimulation was retained. These findings were partially attributed to induction of hepatic microsomal enzymes by isotretinoin. Another study conducted by Lyons et al. (1) showed mild decrease in the indices of thyroid function after treatment with 0.8 mg/kg 13-cis retinoic acid for 3 months. It was noticed that these changes reverted to normal 1 month after discontinuation of therapy. Oral isotretinoin therapy is increasingly used as an effective antiacne medication. It needs to be kept in mind that this drug could have antithyroid effects in susceptible patients. Therefore, there should be a low threshold for checking thyroid function tests in patients taking isotretinoin even if they have subtle signs or symptoms of thyroid dysfunction.

Association of Psychosis and Hyperthyroid Goiter

Sir: Psychiatric symptoms have been reported, not infrequently, with disorders of the thyroid gland,1 most commonly with hypothyroidism. Additionally, psychosis is quite a rare occurrence,2,3 with hyperthyroxinemia being considered a potential cause.4 We present a case of a young man with preceding symptoms of hyperthyroidism and an acute psychotic state. Case report. Mr. A, a 31-year-old married man, was brought to the psychiatry outpatient clinic by his family in March 2003. Around January 2003, he had started reporting subtle complaints in the form of gradually increasing appetite and thirst, loss of weight, mild tremors, and occasional nervousness without any apparent reason. Around February 2003, he started remaining tense, preoccupied, irritable, and restless, complaining of lack of confidence with poor concentration. Subsequent worsening led to additional features of irrelevant speech, inappropriate affect, paranoid ideas, and auditory hallucinations. Mr. A was premorbidly well-adjusted, with no significant medical or surgical history or any history of substance abuse. There was family history of hypothyroidism in the mother and bipolar affective disorder in the father. Physical examination showed moist palms, fine tremors of fingers, and exaggerated deep tendon reflexes in all the limbs. Mr. A had a soft, diffusely enlarged thyroid gland. Investigations found high triiodothyronine/thyroxine levels, low thyroid-stimulating hormone levels, and high radioactive iodine uptake at 4 hours that became low at both 24 and 48 hours. Ultrasound of the thyroid revealed bilateral symmetrical enlargement of both lobes and isthmus, with multiple tiny nodules. Test for thyroid microsomal antibody was positive. The endocrinologist made a diagnosis of diffuse toxic goiter and advised nonsurgical treatment. Initially, Mr. A was treated with risperidone, clonazepam, and trihexiphenidyl as an outpatient. However, due to nonre-sponse he had to be managed as an inpatient. Olanzapine (10–20 mg/day), lorazepam (4–8 mg/day intravenously/oral), and zolpidem (10 mg nocte) were used for treating psychosis, with carbimazole (40 mg daily) and atenolol (50 mg daily) for hyperthyroidism. Mr. A showed improvement in all the symptoms over the next 7 to 10 days, and the symptoms were negligible after around 4 weeks, except for occasional apprehension regarding his office work. Mr. A was discharged in a stable condition with recommendations to visit psychiatric and endocrinology outpatient clinics and to continue with medicines. His diagnosis at that time was organic delusional (schizophrenia-like) disorder (ICD-10 criteria).5 After discharge, Mr. A maintained euthyroid status (with medication). He was followed up in the psychiatry outpatient clinic. There was no emergence of psychosis; his antipsychotic was tapered and stopped after 6 months. Mr. A was asymptomatic at last follow-up (8 months post-discharge). Patients with elevated thyroid hormonal levels frequently have psychological symptoms and sometimes have well-defined psychotic syndromes, as described above in our index patient. The pattern and association of onset and resolution of symptoms with treatment response in our patient point to the likelihood that the psychosis was secondary to the hyperthyroid state. Case reports refer to certain manifestations, i.e., thyrotoxic psychosis,2 organic schizophreniform disorder in autoimmune thyroiditis,6 and psychosis following acute alteration of thyroid status.7 It is important to distinguish these cases from the transient hyperthyroxinemia that may accompany acute exacerbations of certain psychiatric disorders,8 as the distinction can have important implications for management. As in our index case, most people with a psychotic illness induced by hyperthyroxinemia may respond well to a combination of short-term antipsychotic treatment and management of the underlying thyroid illness.3,9 Other researchers have put forward a case for studying neuropsychiatric aspects of thyroid disorders.3,9 We affirm this suggestion, highlighting the need for a close liaison between psychiatrists and endocrinologists.

Influences of Age, Gender, Smoking, and Family History on Autoimmune Thyroid Disease Phenotype

Both genetic and environmental factors contribute to susceptibility to Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as disease manifestations. The objective of the study was to define how endogenous/environmental factors contribute to variation in phenotype. This was a multicenter cohort study. PATIENTS/OUTCOME MEASURES: We prospectively collected clinical/biochemical data as part of the protocol for a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian subjects, whether age at diagnosis, gender, family history (FH), smoking history, and presence of goiter influenced disease manifestations. For 2405 subjects with GD, the presence of goiter was independently associated with disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and current smoking (P < 0.001) were both independent predictors of the presence of ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of males) and HT (n = 400) (56.4% of females, 51.7% of males) reported a FH of thyroid dysfunction. In GD, a FH of hyperthyroidism in any relative was more frequent than hypothyroidism (30.1 vs. 24.4% in affected females, P < 0.001). In HT, a FH of hypothyroidism was more common than hyperthyroidism (42.1 vs. 22.8% in affected females, P < 0.001). For GD (P < 0.001) and HT (P < 0.05), a FH was more common in maternal than paternal relatives. The reporting of a parent with thyroid dysfunction (hyper or hypo) was associated with lower median age at diagnosis of both GD (mother with hyperthyroidism, P < 0.001) and HT (father with hypothyroidism, P < 0.05). In GD and HT, there was an inverse relationship between the number of relatives with thyroid dysfunction and age at diagnosis (P < 0.01). Marked associations among age at diagnosis, disease severity, goiter, ophthalmopathy, smoking, and FH provide evidence for interactions between genetic and environmental/endogenous factors; understanding these may allow preventive measures or better tailoring of therapies.