Effect of Adequate Thyroid Hormone Replacement on the Hypothalamo-Pituitary-Gonadal Axis in Premenopausal Women with Primary Hypothyroidism.

BACKGROUND: While the effects of thyroxine (T4) replacement on improving gonadal function in hypothyroid men has been well documented, the same has not been adequately studied in hypothyroid premenopausal women. METHODOLOGY: Premenopausal women with overt hypothyroidism (thyroid-stimulating hormone [TSH] > 15 IU/L) were tested in the early follicular phase of their natural menstrual cycles or after a progesterone challenge for gonadotropins, estradiol (E2), and prolactin (PRL). They were then treated adequately with T4 replacement and retested under similar circumstances for the same parameters ≥2 months after the restoration of euthyroidism. RESULTS: Forty premenopausal hypothyroid women were evaluated at baseline and ≥2 months after adequate T4 replacement. At baseline, there was an inverse correlation of the gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and TSH, prolactin (PRL) and free T4 (fT4), and E2 and PRL. After normalization of the thyroid function, there was a significant fall in PRL (p < 0.001) accompanied by a rise in serum E2 (p < 0.001). There were no changes in the levels of the gonadotropins LH and FSH. The proportion of patients with hyperprolactinemia fell 5-fold, from 5/40 to 1/40. While there were 5 patients with low estrogen prior to treatment, there were none with hypoestrogenemia after treatment. CONCLUSION: Hypothyroidism is associated with a reversible partial suppression of the hypothalamo-pituitary-gonadal axis in premenopausal women, demonstrated by lower E2 along with a mild elevation of PRL. Treatment of hypothyroidism improves the level of estrogen and lowers the level of PRL.

Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance.

BACKGROUND: Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism. MATERIALS AND METHODS: A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase. RESULTS: DHEAS was found to be higher in the nonobese patients as compared to the obese (p = 0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IR< 2.3) (p = .06).While the total testosterone (p = .044) and SHBG (p = .007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p = .005). CONCLUSIONS: The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.

Atypical Parathyroid Adenoma with Multiple Brown Tumors as Initial Presentation: A Rare Entity.

Brown tumors seen in hyperparathyroidism are rare, non-neoplastic lesions because of abnormal bone metabolism, and they can mimic benign bone tumors or malignancy. Although biopsy is considered as the gold standard for diagnosis, it can be inconclusive. As the diagnosis of brown tumors is often challenging, a high index of suspicion is essential for diagnosis. We present a case of 21-year-old woman who presented with multiple painful bony lesions, which were initially misdiagnosed as fibrous dysplasia. Due to persistent bone pain and deterioration in her physical mobility, she was referred to tertiary care centre. After thorough clinical workup, she underwent Tc-99m methylene diphosphonate bone scintigraphy that raised strong clinical suspicion of hyperparathyroidism and brown tumors. Subsequently, Tc-99m-methoxy isobutyl isonitrile (MIBI) parathyroid scintigraphy revealed a solitary MIBI avid focal lesion, suggestive of left inferior parathyroid adenoma. Later parathyroidectomy was performed and histopathological examination confirmed it as atypical parathyroid adenoma.