Avraham Ishay

Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism.

OBJECTIVE To evaluate the effect of parathyroidectomy on metabolic abnormalities associated with cardiovascular disease in patients with primary hyperparathyroidism (PHPT). METHODS Thirty-four patients with PHPT (aged 51.0 ± 11.8 years, mean ± standard deviation) underwent assessment before and 1 year after successful parathyroidectomy. A control group of 42 normocalcemic healthy subjects, matched for age and body mass index, was also examined at baseline. We measured serum lipids, glucose, insulin, uric acid, calcium, parathyroid hormone, C-reactive protein, and bone density. Insulin resistance index was evaluated by homeostasis model assessment, and the presence of metabolic syndrome was determined. Because of multiple tests, the level of statistical significance was set at .01. RESULTS After parathyroidectomy, there was a decrease in diastolic blood pressure (P<.02) and in serum concentrations of uric acid (P<.04) and insulin (P<.009). No difference was observed in rates of metabolic syndrome in patients before and 1 year after parathyroidectomy (23.5% versus 17.6%; P>.46). Insulin resistance index values were also unchanged from before to after parathyroidectomy (1.3 ± 0.9 and 1.1 ± 0.9, respectively; P>.68). A substantial increase in spine bone density (5%; P<.05) was noted postoperatively. Multivariate logistic regression analysis, after adjustment for age and body mass index, revealed that parathyroidectomy did not lead to a significant decrease in likelihood of cardiovascular risk-odds ratio (OR), 1.82; 95% confidence interval (CI), 0.53 to 6.21 (P>.34) for the metabolic syndrome and OR, 0.82; 95% CI, 0.17 to 3.88 (P>.8) for the insulin resistance index. CONCLUSION In this study, surgical treatment had no beneficial effect on cardiovascular risk, as assessed by the metabolic syndrome and insulin resistance markers in patients with PHPT 1 year after parathyroidectomy.

Increased 6-sulfatoxymelatonin excretion in women with polycystic ovary syndrome.

OBJECTIVE To determine melatonin production in hyperandrogenic women. DESIGN Controlled prospective study. SETTING Outpatients in an academic medical center. PATIENT(S) Twenty-two women with polycystic ovary syndrome (PCOS), 20 women with idiopathic hirsutism, and 15 age-matched individuals who had similar body mass indexes as controls. INTERVENTION(S) Fasting blood samples and 24-hour urinary samples were obtained from all participants. MAIN OUTCOME MEASURE(S) All participants provided serum samples for the measurement of LH, FSH, testosterone, E(2), DHEAS, 17 alpha-hydroxyprogesterone (17-OHP), and insulin levels, as well as urinary 6-sulfatoxymelatonin (aMT6s). RESULT(S) Women with PCOS had higher aMT6s, testosterone, LH/FSH ratio, and insulin values than either women with idiopathic hirsutism or control women. Testosterone inversely correlated with aMT6s in PCOS. Regression analysis revealed that only testosterone was an important determinant of aMT6s in PCOS. CONCLUSION(S) Women with PCOS have increased melatonin production.

Combined Adrenal Myelolipoma and Medullary Hyperplasia

Objective: A patient is reported with hypertension due to combined medullary adrenal hyperplasia and myelolipoma. Methods: A 52-year-old woman with long-standing hypertension was evaluated for an incidentally discoveredlargetumor of the left adrenal. Left adrenalectomy was performed for a presumptive clinical diagnosis of pheochromocytoma. Results: Histopathologic examination revealed a mixed tumor consisting of a large myelolipoma with infiltrating foci of adrenal medulla. Conclusions: A patient is described with hypertension, myelolipoma and adrenal medullary hyperplasia; following adrenalectomy, however, blood pressure and biochemical abnormalities normalized.

Minimally Invasive Follicular Thyroid Carcinoma Developed in Dyshormonogenetic Multinodular Goiter Due to Thyroid Peroxidase Gene Mutation

BACKGROUND The occurrence of thyroid carcinoma in patients with congenital hypothyroidism (CH) caused by dyshormonogenesis is very rare, and has only been reported in one patient harboring mutations in the thyroid peroxidase (TPO) gene. PATIENT FINDINGS We report on a 29-year follow-up of two consanguineous siblings with CH due to total iodide organification defect who also had sensorineural hearing loss. Molecular analysis revealed a novel biallelic mutation of the TPO gene in which phenylalanine substitutes serine at codon 292 (c.875C>T, p.S292F) in exon 8. Despite early initiation, adequate doses of levothyroxine treatment and consequently normal thyrotropin (TSH) levels, the proposita developed a huge multinodular goiter (MNG) and underwent total thyroidectomy due to tracheal compression. Pathological examination revealed a unifocal follicular thyroid carcinoma without vascular invasion in the left lobe of the thyroid gland. SUMMARY Our finding of follicular thyroid carcinoma arising from dyshormonogenetic MNG in a patient without elevated serum TSH levels indicates that genetic and environmental factors other than TSH level might be involved in the development of thyroid carcinoma in dyshormonogenetic MNG. CONCLUSIONS Despite the rare occurrence of thyroid carcinoma in dyshormonogenetic MNG, we recommend long-term follow-up and regular neck ultrasound imaging to prevent delayed diagnosis of thyroid carcinoma.

Pheochromocytoma due to unilateral adrenal medullary hyperplasia

We describe two male patients, aged 17 and 47 years, with clinical and biochemical features of pheochromocytoma. Both patients had normal‐sized adrenal glands on abdominal CT scan and abnormal unilateral uptake of I‐123 metaiodobenzylguanidine (MIBG) on scintigraphy. The surgical adrenalectomy revealed normal macroscopic glands in both patients. Histological examination showed adrenal medullary hyperplasia with adrenal cortico‐medullary ratios of 2 : 1 and 4 : 1. Unilateral adrenalectomy resulted in amelioration of symptoms and normalization of catecholamines excretion. DNA examination for RET proto‐oncogene revealed no mutations in exons 10, 11, 13, 14 and 16. Our results suggest that diffuse adrenal medullary hyperplasia may be the initial pathological change in the adrenal gland leading, subsequently, to the development of nodular hyperplasia and adrenal medullary tumor. These results indicate that the syndrome of pheochromocytoma may occur as an unilateral adrenal medullary hyperplasia in patients without evidence for multiple endocrine neoplasia.

SERUM THYROGLOBULIN LEVELS AFTER FINE-NEEDLE ASPIRATION OF THYROID NODULES

OBJECTIVE To investigate whether a minor insult to the thyroid gland attributable to fine-needle aspiration (FNA) or external thyroid palpation can cause a release of serum thyroglobulin (Tg) into the circulation. METHODS We determined serum Tg levels before and at 60 minutes and 15 days after FNA in 25 patients with thyroid nodules. Results were compared with those obtained in 25 patients with thyroid nodules, in whom serum Tg concentrations were determined before and 60 minutes after palpation of the thyroid, and in 15 healthy subjects without thyroid disease, who had no thyroid palpation and no FNA, from whom 2 blood specimens were obtained 60 minutes apart. All participants had normal results of thyroid function tests and no detectable antithyroglobulin or thyroid peroxidase antibodies. RESULTS After FNA, 22 of 25 patients had significant elevation of serum Tg concentrations. The Tg levels returned to baseline values 15 days after FNA. In 4 of the 25 patients with thyroid nodules who had palpation of the thyroid, a significant increase in serum Tg levels was elicited. None of the 15 healthy subjects with normal thyroid glands (and with no FNA or thyroid palpation) had significant Tg elevations. CONCLUSION FNA causes a significant increase in serum Tg concentrations, which may persist for 15 days. Therefore, Tg assay should not be scheduled prematurely after FNA.

Color-flow doppler sonography in patients with subclinical thyroid dysfunction.

OBJECTIVE To assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction. METHODS In this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal se-rum free thyroxine (FT4) and free triiodothyronine (FT3) in the presence of high (subclinical hypothyroidism), or low-suppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT4, FT3, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroid-ism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements. RESULTS The study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 +/- 5.6 cm/s vs 15.7 +/- 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 +/- 10.7 cm/s vs 21.9 +/- 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P<.001] and 53% vs 15%; [P<.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity. CONCLUSION We have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction.

Beclomethasone dipropionate enema in ulcerative colitis: Is it safe?

Objective: To evaluate the pituitary-adrenal axis (PA axis) reserve in patients with ulcerative colitis (UC) treated with steroid enemas, we performed 1mug ACTH test.Methods: Patients with UC (n=8) given beclomethasone dipropionate enema (Betnesol) for 4 weeks. Fasting serum cortisol and the response at 30 and 60 minutes following an IV 1mug ACTH injection were determined after 2 weeks of Betnesol enemas. Patients were retested, one month after discontinuation of enemas.Results: Fasting and peak cortisol responses to ACTH were suppressed in six patients. Additional patient had suppressed fasting cortisol and another patient had blunted response to ACTH. One month off Betnesol enema, basal and peak cortisol response to ACTH were normal in all but one patient.Conclusion: Betnesol enemas are associated with severe suppression of the PA axis in almost all patients. Caution is required in patients with UC after withdrawal of rectal steroids as adrenal insufficiency can occur.

Subcutaneous calcification in a patient with postsurgical hypoparathyroidism

We describe a patient with painful swelling of a distal tuft, which was associated with hypoparathyroidism and the prolonged use of calcium salt and vitamin D. A 45year-old woman was evaluated for a painful red and tender second distal tuft of 1-year’s duration. Past medical history revealed that she had hypothyroidism and hypoparathyroidism after a total thyroidectomy performed in 1994 for benign nodular goiter. She was treated with L-thyroxine (0. 100 mg/day), calcium gluconate (1500 mg/day) and vitamin aD3 (1 lg twice daily). Follow-up of serum calcium and urinary calcium excretion was conducted periodically and revealed normal values over the last 5 years. However, serum phosphorus levels were elevated on several occasions to 4. 7–5. 0 mg/dl. The patient was seen 3 years prior to the present visit because of painful and swollen hands. At that time there was no clinical or laboratory evidence suggesting an autoimmune disorder. Skin biopsy and hand radiographs (Fig. 1A) revealed no abnormality. A diagnosis of osteoarthritis was made. At the present visit there was no history of systemic involvement, nor were there any significant findings on general physical examination. Musculoskeletal examination revealed an extremely tender, swollen and red distal second tuft in the right hand. Laboratory examination revealed normal serum TSH (0. 15 mIU/ml), free T4 (1. 7 ng/dl), calcium (8. 8 mg/dl), 24 h urinary calcium excretion (220 mg/24 h). Serum phosphorus level was elevated (4. 7 mg/dl). An autoimmune panel including antinuclear antibodies, anti-DNA antibodies, extractable nuclear antigens, complement levels, anticardiolipin antibodies and rheumatoid factor were all negative. Radiographs of the hands showed a thick large calcification of the affected tuft (Fig. 1B). A smaller faint calcification was observed at the subcutaneous tissue overlying the wrist. The spectrum of diseases involving localized subcutaneous calcification includes scleroderma, CREST syndrome, SLE, primary hyperparathyroidism, idiopathic hypoparathyroidism and congenital hypoparathyroidism [1, 2, 3]. Excessive ingestion of vitamin D and calcium in patients with chronic renal failure and reduced protein C may lead to calciphylaxis, a situation of multiple nodular subcutaneous calcifications [1, 2, 3, 4]. Chronic hypocalcemia is treated with calcium salts and vitamin D, given as aD3. The goals are to relieve symptoms and raise and maintain the serum calcium levels in the low–normal range. Treatment also lowers the serum phosphorus levels in patients with hypoparathyroidism. Hyperphosphatemia, when it occurs, can induce metastatic calcifications by exceeding CA x P physiochemical solubility production [5]). The occurrence of intermittent hyperphosphatemia in our patient suggest that therapy was suboptimal, resulting in subcutaneous calcification [6]. Our case is the first description of acquired hypoparathyroidism due to the prolonged use of calcium and aD3 associated with subcutaneous calcification.

Infertility and bilateral adrenal tumors

An infertile man who presents with azoospermia and bilateral adrenal tumors reveals an XX karyotype and congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hysterectomy and bilateral oophorectomy performed in infancy and lack of treatment resulted in full masculinization.