The influence of aging on serum LH and testosterone (T) pulse frequency and gonadotroph sensitivity to androgen and estrogen feedback was studied in young (less than 55 yr old) and elderly (greater than 65 yr) Trappist monks. LH pulse frequency (sampling interval, 20 min) was significantly lower [0.25 +/- 0.03 (+/- SEM) vs. 0.38 +/- 0.02 pulses/h; P less than 0.01] in elderly (n = 21) than in young monks (n = 27); the pulse amplitudes were similar. Similarly, T pulse frequency was lower in the elderly than in the young monks (0.13 +/- 0.04 vs. 0.23 +/- 0.02 pulses/h; P less than 0.01). In elderly men, the hypothalamo-pituitary complex was more sensitive to 5 alpha-androstan-17 beta-ol-3-one feedback, as determined by the decrease in serum LH and T levels. Moreover, during 5 alpha-androstan-17 beta-ol-3-one (125 mg/day, percutaneously, for 10 days) administration, the LH response to LHRH (100 micrograms, iv) was significantly higher in the elderly men compared to the pretreatment response. During estradiol (1.5 mg/day, percutaneously for 10 days) administration, the LH response to LHRH was decreased in the elderly men, but unchanged in the young men, suggesting greater responsiveness to estradiol in the elderly men. We conclude that in aged men, decreased testicular androgen secretion is not exclusively the consequence of a primary testicular alteration, but that important changes occur in hypothalamo-pituitary function, specifically decreased LH pulse frequency and increased LH responsiveness to sex hormone feedback.
Seven patients with hyperthyroidism due to a TSH-secreting pituitary macroadenoma have been observed of a total of 800 patients with pituitary tumors over a period of 15 yr. Serum TSH levels varied between 1.1-36.3 mU/L. The serum alpha-subunit level was low in 1 case, while in 4 other cases the concentration was elevated and varied between 3.7-7.8 micrograms/L. Serum TSH beta levels were normal in the 4 cases in which it was determined. Serum GH or PRL levels were elevated in 5 cases. In 1 patient the cosecretion of TSH, GH, and PRL was confirmed by immunocytochemical examination. Serum TSH and alpha-subunit responses to TRH, GnRH, CRF, GRF, dexamethasone, methimazole, T3, and bromocriptine administration were variable when studied. Serum TSH and alpha-subunit circadian rhythms were absent in 1 case and inverted in another. A serum alpha-subunit pulsatility without TSH pulses was observed in 1 patient. Five patients underwent transsphenoidal adenomectomy. Three of 4 patients operated on in our center were cured, but a recurrence of the adenoma was found in 1 of them after 5 yr. The fifth patient was not cured. Treatment with octreotide in 3 patients resulted in normalization of serum TSH, GH, and thyroid hormones levels. Cosecretion of PRL in 1 case and alpha-subunit in 2 cases was also inhibited. Partial tachyphylaxis occurred in 1 patient. In summary, heterogeneity in clinical presentation, hormonal expression, and therapeutic response appears to characterize these TSH-secreting adenomas.
In a national screening program for neonatal hypothyroidism, our criterion for diagnosis is a plasma TSH value exceeding 40 microunits/ml on the fifth day of life. Excluding cases with obvious thyroid abnormalities, we identified a group of 14 neonates with unexplained plasma TSH elevation out of 10,261 screened. The mothers of these infants also exhibited high plasma TSH immunoreactivity; both mother and child in these instances were clinically euthyroid. The material responsible for this TSH immunoreactivity had the following characteristics. After parturition, it disappears from circulation within 2 months in the infants and within 4-6 months in the mother, its apparent molecular weight approximated 150,000 daltons, and its affinity for protein A-Sepharose and its binding properties suggested that the material was an immunoglobulin. Binding is observed typically for heterologous immunoglobulin and human TSH. The heterophilic character of these immunoglobulins explains their interference in many RIA systems, including the TSH RIA commonly used in neonatal screening programs for hypothyroidism.
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