A B S T R A C T Studies on peripheral metabolism of simultaneously administered 125I-labeled L-thyroxine (['I1]T4) and "1'I-labeled L-triiodothyronine ([.1.I]T3) were performed in five normal subjects, in four patients with untreated hypothyroidism, and in 3 hypothyroid patients made euthyroid by the administration of T4. The fractional turnover rate (Xos) of thyroid hormones irreversibly leaving the site of degradation and the volumes of pool 1 (serum, Vi), of pool 2 (interstitial fluid, V2), and of pool 3 (all tissues, V3) were obtained by using a three-compartment analysis. In addition to the turnover studies, the ratios for the in vivo To to T3 conversion were determined by paper chromatographic study in sera obtained 4, 7, and 10 days after the injection. The rate (K12) of the extrathyroidal conversion of T4 to T3 was also estimated by the compartment analysis. The T3 distribution volume (V3) of pool 3, in which T3 is utilized and degraded, was about 60% of total distribution volume (V = V1 + V2+ V3) in normal subjects, whereas only about 25% of the extrathyroidal T4 pool was in the intracellular compartment, indicating that T3 is predominantly an intracellular hormone. The V3/V ratios of T3 were almost constant in a normal ratio of about 60% in hypothyroid patients before and after treatment. On the other hand, the V3/V ratios of T4 were elevated in patients with untreated hypothyroidism, and they returned almost to the normal range after administration of T4. Thus, the V3/V ratio of T4 bore a significant inverse relation to the free T4 concentration in all subjects (r = -0.68, P < 0.05). The findings suggested a redistribution of T4 into the cellular compartment in patients with untreated hypothyroidism. In normal subjects values for K12 averaged 3.00±0.68% per day of the extrathyroidal T4 pool, and the amount of T3 generated by the conversion of T4 (mean-SD, 17±5 Mg/day) was found to contribute approximately 70% of the daily T3 production (mean +SD, 24±5 /Lg/day). The patients with untreated hypothyroidism had elevated Ku2 (mean+SD, 4.16+0.72% per day). Because of diminution of extrathyroidal T4 pool, the amount of T3 converted from T4 was markedly diminished in the untreated patients (mean+SD, 4+3 jug/day), and it agreed closely with T3 production rate (mean±+SD, 3±2 Mg/day). In the patients treated with T4 K,2 returned almost to the normal range (mean±SD, 2.59+0.47% per day), and the amount of T3 arising from deiodination of T4 (mean±+SD, 24±6 Mg/day) corresponded closely to T3 production rate (mean+SD, 21±5 jug/day). Furthermore, a highly significant correlation was evident in the plots of serum T3 concentrations against the amounts of T3 generated by the conversion of T4 in all subjects (r = + 0.85, P < 0.001). The results indicated that the amount of T3 formed by the extrathyroidal conversion of T4 is a major determinant of serum T3 concentration in normal subjects and in patients with hypothyroidism before and after treatment.

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A 57-year-old male, who had been suffered from hypertension and diabetes mellitus for 10 years, was admitted to the hospital because of thirst, lassitude and muscle wasting. On admission, his urinary excretion of 17-OHCS and plasma cortisol levels were elevated without diurnal variations. Plasma ACTH levels were found to be very low with repeated determinations. Dexamethasone suppression test, 2 mg 4 times a day orally for 2 days, showed no changes in plasma cortisol levels and only a mild reduction in urinary 17-OHCS excretion. Estimation of urinary catecholamines showed an increase only in norepinephrine. Abdominal computerized tomography and radionuclide scanning of adrenal glands with 131I-adosterol demonstrated a well-defined adrenal mass in the left side without apparent changes in the right side. 131I-metaiodobenzylguanidine scintigraphy was negative. At surgery, his left adrenal medulla was found to be hypertrophic in addition to the cortical tumor. The left adrenal gland was also removed. After surgery, excretion of urinary catecholamines fell to nearly the normal range and he was discharged without insulin and antihypertensive drugs. Microscopically, the cortical tumor is an adenoma consisting of lipid laden cells and eosinophilic compact cells. Medullary cells were distinctly hyperplastic in appearance and many of the cells were extensively vacuolated, suggesting an active functional status. The present report describes a patient with Cushing's syndrome who showed increased urinary catecholamine excretion due to the possible coexistence of adrenal medullary hyperplasia. As far as we know, this is the first case of Cushing's syndrome with this abnormality.

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