Papillary thyroid carcinoma, parathyroid adenoma, and unexplained hypercalcitoninemia: an unusual presentation of multiple endocrine neoplasia type 2A?

Multiple endocrine neoplasia type 2 (MEN 2) is a rare syndrome of medullary thyroid carcinoma (MTC) with pheochromocytoma and/or primary hyperparathyroidism (PHP), usually due to multigland hyperplasia. MEN 2 is associated with several RET protooncogene mutations. A 61-year-old woman with a family history of RET-positive MTC presented with a solitary thyroid nodule. Fine-needle aspiration biopsy was suspicious for neoplasm. Biochemical studies revealed basal hypercalcitoninemia (116 pg/mL [normal <26]) and PHP (serum calcium, 10.9 mg/dL; intact PTH, 113.2 pg/mL [10.0-65.0]). Pheochromocytoma screening was negative. A provisional diagnosis of MEN 2 was made, but at surgery, a single parathyroid adenoma was resected and frozen sections of several lymph nodes revealed papillary thyroid carcinoma (PTC). A total thyroidectomy was performed. Final histological diagnosis was PTC and parathyroid adenoma with no evidence of MTC. Postoperatively, RET mutation testing was positive. The basal calcitonin (CT) fell to 25 pg/mL, but peaked at 935 (normal <105) after pentagastrin infusion, consistent with occult MTC. After radioiodine ablation, CT decreased further. Octreotide scanning was negative. Faced with PHP, a thyroid nodule, and a family history of MTC, clinicians tend to diagnose MEN 2. This patient had a single parathyroid adenoma and nonmedullary thyroid cancer, which the literature actually suggests to be an association more frequent than MEN 2. Yet, there remains compelling data in favor of occult MTC, leaving open the possibility of an MEN 2 variant with the rare association of PTC.

The effect of endurance training on serum triiodothyronine kinetics in man: physical conditioning marked by enhanced thyroid hormone metabolism.

OBJECTIVE: We studied the relationship between endurance training, aerobic capacity, and T3 metabolism in healthy euthyroid men. DESIGN: T3 kinetic studies performed on two groups of subjects differentiated on the basis of physical activity status and aerobic capacity. SUBJECTS: Five endurance-trained athletes and five sedentary controls (mean +/- SD VO2 max = 48.2 +/- 7.1 vs 23.2 +/- 4.5 ml/kg/min, respectively) matched for age, body surface area, lean body mass, and baseline thyroid function. MEASUREMENTS: Kinetic analysis performed using serial serum T3 levels measured following oral T3 administration. Metabolic clearance rate, total volume of distribution, disposal rate, and total body pool calculated using non-compartmental analysis. RESULTS: When normalized for lean body mass, all kinetic parameters were 25-38% greater in the athletic group compared to controls (P < 0.05). Total volume of distribution, disposal rate, and total body pool were positively correlated with aerobic capacity (r = +0.69 to +0.79; P < 0.05). Metabolic clearance rate was positively correlated to a non-significant degree. CONCLUSIONS: These results confirm the findings of prior studies that thyroid hormone metabolism is altered by physical conditioning. In addition, we demonstrated a positive correlation between aerobic capacity and several parameters of T3 kinetics. Differences in absolute lean body mass cannot explain these findings; rather it appears that there is something qualitatively different in the way endurance-trained tissue processes thyroid hormone, compared to untrained tissue. The study was not designed to elucidate these differences at the cellular level; however, it does support a link between muscle physiology and T3 activity and may suggest a physiological role for thyroid hormone in physical conditioning.

Euthyroid thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis (TPP) is a dramatic complication of thyrotoxicosis usually seen in young men with untreated Graves' disease. We report the case of a 29-year-old active duty man with TPP attacks atypical in that they occurred during and after resolution of the hyperthyroidism. Our literature review revealed only two previously reported cases of TPP concurrent with euthyroidism. Risk factors for TPP include the postprandial state after carbohydrate-rich meals and the post-exertional state. At least a 2-week "window of vulnerability" for TPP appears to exist after initiation of antithyroid therapy. Hyperthyroid active duty males are especially at risk of TPP, and require physical profiling at the time of diagnosis and for a limited period after they become euthyroid, to minimize the occurrence of this complication.

Severe systemic reactions to typhoid vaccination: two cases and a review of the literature.

Typhoid vaccination is part of the routine immunization of all military personnel on mobility status. We report the cases of Air Force students who presented to our facility with presumed systemic reactions to the typhoid vaccine much more severe than those commonly reported. Review of the literature reveals that an influenza-like reaction of variable severity commonly occurs in these patients, and in addition there are isolated reports of more severe reactions. These findings shed doubt on the overall safety of the currently used vaccine and warrant a consideration of its abandonment. Several safer alternatives, including the new live oral vaccine used in Europe, are discussed.