Richard C. Dimond

Glucose modulation of alterations in serum iodothyronine concentrations induced by fasting.

In order to investigate the process by which dietary composition may regulate T4 conversion to T3 and reverse T3, iodothyronine levels were measured in the sera of seven obese subjects during consecutive study periods. These study periods included the ingestion of an approximate weight-maintaining diet (40% carbohydrate, 40% fat, 20% protein) during a control period of 4 days, a fast of 7 days thereafter, and then a 5-day period of glucose ingestion (50 g/day) only. The mean (±SE) serum T3 concentration was 117 ± 8 ng/dl on day 4 of the control period, and gradually decreased to 66 ± 11 ng/dl (p < 0.01) on the last day of fasting. The subsquent administration of glucose was associated with an increase in the mean serum T3 level to 94 ± 10 ng/dl (p < 0.01). Mean (±SE) serum levels of reverse T3 varied reciprocally and were 52 ± 9 ng/dl, 82 ± 12 ng/dl (p < 0.005), and 65 ± 9 ng/dl (compared to fasting, p < 0.05) during the fed and fasting states and during glucose administration, respectively. Furthermore, employing a similar protocol in a different group of subjects, serum sampled during the administration of 100 g of fructose orally during days 8–12 of fasting also was associated with an increase in mean serum T3 and a decrease in mean serum reverse T3, as compared to values obtained on day 6 or day 7 of fasting (T3: 83 ± 6 ng/dl, fasting vs. 111 ± 10, fructose (p < 0.05); rT3: 56 ± 9, fasting vs. 42 ± 6 ng/dl, fructose (p < 0.025)). Serum T4 concentrations were not significantly altered in any study period either during glucose or fructose ingestion. Despite the decrement in serum T3 levels observed during fasting, the mean peak TSH in response to TRH stimulation in a group of 15 obese subjects was decreased during fasting as compared to the fed state (8.1 ± 1.2 μU/ml, fast vs. 12.8 ± 2.0 μU/ml, fed). These observations suggest that both glucose and fructose are capable of modulating serum T3 and reverse T3 levels and that administration of these hexoses in doses of only 100–200 g/day for 5 days may be effective in altering T4 degradative pathways. Furthermore, despite the decreased serum T3 levels, the TSH response to TRH stimulation is decreased, paradoxically, during fasting.

Nature of suppressed TSH secretion during undernutrition: effect of fasting and refeeding on TSH responses to prolonged TRH infusions

TSH responses to 4-hr continuous TRH infusions of approximately 0.8 microgram/min were assessed during feeding (1500 Kcal), fasting, and refeeding (1500 Kcal) intervals in 9 euthyroid obese subjects. The total area under the TSH response curve was 1854 +/- 322 muU/ml . 4-hr during feeding, decreased to 1359 +/- 199 muU/ml . 4-hr (p less than 0.01) on the 10th day of fasting, and remained low, being 1405 +/- 185 muU/ml . 4-hr, despite refeeding a 1500 Kcal diet (40% carbohydrate, 40% fat, 20% protein) for 5 days. Baseline serum T3 concentrations were 167 +/- 11 ng/dl during feeding, 86 +/- 8 ng/dl during fasting, and 119 +/- 12 ng/dl during refeeding. The observed decreases in TSH release appeared to correlate with decreased biologic action on the thyroid gland since the net rise in T3 during the infusion was less in fasting and refeeding than in the control (fed) period. Basal serum rT3 levels were 42 +/- 5 ng/dl during feeding, rose as expected to 56 +/- 5 ng/dl during fasting (p less than 0.005), and were completely restored to normal during refeeding (36 +/- 5 ng/dl). These data suggest that: (1) TSH responsiveness to prolonged TRH infusion is diminished during fasting and does not return to control (fed) values despite 5 days of refeeding a 1500 Kcal diet; (2) net T3 increases observed during the TRH infusion are greater in the fed period than in the fasting or refeeding periods; and (3) 5 days of refeeding a 1500 Kcal diet (40% carbohydrate, 40% fat, 20% protein) did not return the T3 to its original fed value whereas rT3 was completely restored to control values. Lastly, since the TSH response was lower both during the early and late phases of the infusion, the decrease in delta TSH to a bolus of TRH during fasting appears to represent one manifestation of a more general suppression of TSH neogenesis associated with caloric deprivation.

Absent prolactin response to l-tryptophan in normal and acromegalic subjects☆

Abstract l -tryptophan (5 g orally), the precursor of serotonin, was administered to 10 patients with acromegaly and eight control subjects. In normal subjects, there was no significant change in serum prolactin after l -tryptophan. In subjects with acromegaly, there was no significant net change in serum prolactin after l -tryptophan relative either to the baseline value before l -tryptophan or to values obtained on a control day without l -tryptophan. Activation of serotoninergic pathways by oral administration of the serotonin precursor l -tryptophan has no effect on serum prolactin in normal or acromegalic subjects.

Parameters of thyroid function in patients with active acromegaly

In order to determine if acromegaly per se may be associated with abnormalities in thyroidal economy, serum thyroxine-binding globulin (TBG), resin T3 uptake, total and free T4, T3, and reverse T3 concentrations were measured in 21 patients with active acromegaly. Mean (+/- SE) total T4, T3, and reverse T3 levels were 7.1 +/- 0.2 microgram/dl, 111 +/- 4 ng/dl, and 45 +/- 2 ng/dl, respectively, and the mean TBG concentration was 3.6 +/- 0.2 mg/dl. Similarly, mean free T4, T3, and reverse T3 concentrations were 2.4 +/- 0.09 ng/dl, 383 +/- 22 pg/dl, and 118 +/- 7 pg/dl, respectively. None of these values is significantly different from normal and the thyrotropin response to thyrotropin-releasing hormone was also normal. In contrast to several earlier reports, these data suggest that parameters of thyroid function are generally normal in patients with active acromegaly.

Amitriptyline-induced suppression of growth hormone in acromegaly ☆

Abstract (1) Amitriptyline (100 mg p.o. daily at bedtime) for 1 month significantly reduced 24 hr mean serum growth hormone in 3 of 5 acromegalic subjects studied (44, 22 and 18% reductions). (2) Amitriptyline-induced suppression of growth hormone occurred primarily in the late afternoon and evening. (3) Amitriptyline delayed the nocturnal rise in serum growth hormone. (4) The clinical usefulness of amitriptyline in treating acromegaly would probably be very limited because of the modest nature of the reductions in serum growth hormone.

The Effects of Pyridoxine on Pituitary Hormone Secretion in Amenorrhea-Galactorrhea Syndromes

Six patients with amenorrhea, five of whom had galactorrhea and elevated PRL levels, were evaluated on a metabolic ward. All had normal sella tomograms, normal thyroid functions, and routine laboratory evaluations. None of the patients had taken any medication in the previous 6 months. On alternate days, five patients received 500 microgram of TRH iv with the measurement of PRL, TSH, FSh, LH, and hGH; 500 mg L-dopa orally with the measurement of PRL, FSH, and LH; a bolus infusion of 300 mg pyridoxine (B6) with measurement of PRL, hGH, TSH, FSH, and LH; and 25 mg chlorpromazine (CPZ) im with the measurement of PRL, LH, and FSH. The patients were then discharged on 600 mg oral pyridoxine/day and were readmitted for a repeat of the complete protocol 21 days later. The patients were continued on 600 mg oral pyridoxine for 3-4 months with monthly evaluations of serum PRL, LH, and FSH levels. These evaluations continued for 3 months after discontinuing pyridoxine. There was no demonstrable change in serum PRL after acute or chronic B6 therapy, mor was there a significant change in the response of PRL to CPZ, L-dopa, or TRH. The mean basal PRL was 97.5 +/- 9.7 ng/ml and after 3-4 months of oral pyridoxine was 97.1 +/- 14.8. In addition, there was no significant change in LH or FSH levels in response to acute or chronic B6, TRH, L-dopa, or CPZ. Neither acute B6 infusion nor chronic B6 therapy had any effect on TSH or the TSH response to TRH. Finally, acute B6 infusion had no effect on hGH levels and there were no paradoxical hGH responses to TRH. Two patients began having regular menses while on chronic pyridoxine. Their hormonal responses did not differ from those of the group, however.

Failure of 3,3′-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation

In order to determine whether elevations in serum 3,3-diiodothyronine (3,3T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3T2 administration and 168 +/- 65 muU/ml during 3,3T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3T2. These observations suggest that elevation of serum 3,3T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.