Administration of human GH to GH-deficient patients has yielded conflicting results concerning its impact on thyroid function, ranging from increased resting metabolic rate to induction of hypothyroidism. However, most studies have been casuistic or uncontrolled and have used pituitary-derived GH of varying purity, often contaminated with TSH. Therefore, we conducted a double blind, placebo-controlled cross-over study of the effect of 4 months of biosynthetic human GH therapy (Norditropin; 2 IU/m2.day) on thyroid function in GH-deficient adults (8 females and 14 males; mean +/- SE age, 23.8 +/- 1.2 yr). One group (I) was euthyroid without T4 substitution (n = 13), whereas the other (group II) received T4 (n = 9). Serum T4 (nanomoles per L) decreased in both groups after GH treatment [group I, 100 +/- 8 (mean +/- SE) vs. 89 +/- 8 (P less than 0.01); group II, 145 +/- 18 vs. 115 +/- 10 (P less than 0.05)]. Conversely, GH treatment caused an increase in serum T3 (nanomoles per L) in both groups [group I, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 (P less than 0.1); group II, 1.7 +/- 0.1 vs. 1.9 +/- 0.1 (P less than 0.05)]. Similar changes were seen in serum free T4 and T3. The serum T3 level during the placebo period of group I was significantly lower than that in an age-matched reference group (P less than 0.02). Serum rT3 (nanomoles per L) was low in group I and decreased significantly, as in group II, after GH treatment [group I, 0.26 +/- 0.02 (placebo) vs. 0.20 +/- 0.02 (GH; P less than 0.01); group II, 0.38 +/- 0.05 (placebo) vs. 0.29 +/- 0.02 (GH; P less than 0.01)]. Serum TSH decreased in both groups during GH therapy, though not significantly. Serum thyroglobulin was unaltered and did not differ from that in the reference group. In conclusion, our data are consistent with a GH-induced enhancement of peripheral deiodination of T4 to T3. GH thus seems to play an important role, either directly or indirectly, in the regulation of peripheral T4 metabolism.

GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused a significant blunting of serum TSH. These findings suggest that GH plays a distinct role in the physiological regulation of thyroid function in general, and of peripheral T4 metabolism in particular.

Active acromegaly is characterized by inappropriate tissue growth, increased mortality, and perturbations of intermediary metabolism. It is, in general, not well described to which extent these disturbances are normalized after treatment of the disease. To further assess basal and insulin stimulated fuel metabolism in acromegaly six patients with monotropic GH excess were each studied approximately 1 month prior to and 2 months after successful selective pituitary adenomectomy and compared to a control population of seven subjects. The studies consisted of a 3-h basal postabsorptive period and a 2-h hyperinsulinaemic (0.4 mU/kg/min) euglycemic clamp and the methods employed included isotopical measurement of glucose turnover, indirect calorimetry, and the forearm technique. When compared to the control subjects the patients with acromegaly were preoperatively and in the basal state characterized by: 1) increased circulating concentrations of GH, insulin, and C-peptide (P less than 0.05); 2) increased plasma glucose (5.9 +/- 0.2 vs. 5.2 +/- 0.2 mmol/L), blood lactate (710 +/- 90 vs. 580 +/- 70 mumol/L), glucose turnover (2.34 +/- 0.12 vs. 1.93 +/- 0.12 mg/kg/min), and plasma lipid intermediates and a decreased forearm glucose uptake (0.06 +/- 0.02 vs. 0.19 +/- 0.04 mmol/L) (P less than 0.05); and 3) a 20% increase in energy expenditure, a 50% elevation of lipid oxidation rates, and a 130% elevation of nonoxidative glucose turnover (P less than 0.05). During the clamp the patients with active acromegaly were substantially resistant to the actions of insulin on both glucose and lipid metabolism. Following pituitary surgery all of these metabolic abnormalities were abolished. We conclude that active acromegaly is characterized by profound disturbances of not only glucose but also lipid metabolism, which in theory may precipitate the increased mortality in this disease. By showing that these abnormalities and the concomitant overall insulin resistance can be completely reversed our results may also have important implications for other insulin-resistant states and for the potential therapeutic use of GH.

Context:Cortisol is an important catabolic hormone, but little is known about the metabolic effects of acute cortisol deficiency.Objective: The objective of the study was to test whether clinical symptoms of weight loss, fatigue, and hypoglycemia could be explained by altered energy expenditure, protein metabolism, and insulin sensitivity during cortisol withdrawal in adrenocortical failure.Design, Participants, and Intervention: We studied seven women after 24-h cortisol withdrawal and during replacement control during a 3-h basal period and a 3-h glucose clamp.Results: Cortisol withdrawal generated cortisol levels close to zero, a 10% decrease in basal energy expenditure, increased TSH and T 3 levels, and increased glucose oxidation. Whole-body glucose and phenylalanine turnover were unaltered, but forearm phenylalanine turnover was increased. During the clamp glucose, infusion rates rose by 70%, glucose oxidation rates increased, and endogenous glucose production decreased. Urinary urea excretion decreased by 40% over the 6-h study period. Conclusions:Cortisol withdrawal increased insulin sensitivity in terms of increased glucose oxidation and decreased endogenous glucose production; this may induce hypoglycemia in adrenocortical failure. Energy expenditure and urea loss decreased, indicating that weight and muscle loss in Addison's disease is caused by other mechanisms, such as decreased appetite. Increased muscle protein breakdown may amplify the loss of muscle protein.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value.The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo-or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.High levels of thyroid hormones in serum due to increased cirulating TBG is a well known feature during normal pregnancy. Various measures of free thyroid hormones have been introduced in order to aid the diagnosis and control of thyroid dysfunction during pregnancy. Earlier investiga¬ tors have claimed that the amounts of free circulat¬ ing hormones are little affected by pregnancy (Burrow et al. 1975;Pekonen & Lamberg 1978;Ekins 1979). Further, serum TSH has been found nearly unaltered too (Burrow et al. 1975;Pekonen & Lamberg 1978).However, due to high serum levels of hCG, FSH and LH possibly interfering in the TSH assay and methodological difficulties in measuring free T4 and free T3 it is still not firmly established whether minor variations in free hormones and TSH occur during normal pregnancy. It is generally accepted that it is important to keep thyroid function near to normality during pregnancy in patients treated for thyroid disease; it is therefore important to know the normal variations. In the present study we have obtained repeated blood samples from normal women during and after pregnancy and taken special methodological precautions to avoid inter¬ ference of other hormones and protein alterations in the assays. Materials and MethodsTwenty healthy pregnant women were asked to partici¬ pate in the investigation at their first visit to their general practitioner for pregnancy control. They constituted a consequtive series of healthy pregnant women contacting a suburb clinic with 4 general practitioners. Excluded were pregnant women who paid their firs...