Central diabetes insipidus preceding acute myeloid leukemia with t(3;12)(q26;p12).

A 52-year-old woman presented with polyuria and polydipsia. A diagnosis of central diabetes insipidus (DI) was made, which turned out to be the first sign of acute myeloid leukemia (AML). Cytogenetic analysis revealed a balanced translocation between chromosome 3 and 12 t(3;12)(q26;p12). The patient was treated with standard induction chemotherapy and vasopressin. Before consolidation chemotherapy could be administered, deep venous thrombosis was diagnosed and leukemia relapsed. Rescue chemotherapy was started. This is the first report of an association between AML with t(3;12) and DI. Its possible pathogenesis is discussed with a review of the literature.

Irreversible gonadal damage in male survivors of pediatric Hodgkin's disease.

BACKGROUND: Gonadal damage in adult patients after chemotherapy for Hodgkin's disease is well documented, but data of patients treated before adulthood are scarce. METHODS: Gonadal and hormonal function were studied in 19 male long term survivors of Hodgkin's disease who were treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP chemotherapy) before (n = 15) or during puberty (n = 4). The studies were performed a median of 10 years after treatment and repeated in the majority of the patients at the time of yearly visits. RESULTS: Germ cell damage was present in all patients. Semen analysis revealed azoospermia in 12 patients and oligospermia in 6; no recovery of spermatogenesis was seen at follow-up. Testicular size was small in all but one patient. Follicle-stimulating hormone levels were elevated (mean, 14.4 +/- 7.8 U/l) and increased over time (mean, 21.1 +/- 10.5 U/l, P < 0.001). In seven patients, luteinizing hormone (LH) was elevated, indicating Leydig cell dysfunction; also in four of those patients, plasma testosterone was decreased. In three other patients, the response of LH to gonadotropin-releasing hormone was exaggerated with a normal basal LH and testosterone. Comparing testicular function of prepubescent versus pubescent state at time of treatment appears to show a trend for improved outcome in the younger patients. CONCLUSIONS: Gonadal function of long term survivors of pediatric Hodgkin's disease treated with MOPP chemotherapy is severely impaired permanently.

Pulsatile thyrotropin secretion in patients with Cushing's syndrome.

Pulsatile and circadian thyrotropin (TSH) secretion were studied in 16 healthy controls and in three patients with Cushing's syndrome who were studied twice (before and after treatment). Blood was sampled every 10 minutes over 24 hours for TSH (immunoradiometric assay [IRMA]). Mean 24-hour TSH in Cushing's syndrome was lower than in controls (0.4 +/- 0.2 v 1.7 +/- 0.7 mU/L, P < .001), related to a lower mean 24-hour TSH pulse amplitude (Desade: 0.16 +/- 0.15 v 0.44 +/- 0.20 mU/L, P < .001; Cluster: 0.17 +/- 0.14 v 0.39 +/- 0.20 mU/L, P < .001; mean +/- SD). TSH pulse frequency was unchanged with approximately 10 pulses/24 h. The nocturnal TSH surge was diminished relative to controls (median-0, range- -0.03 to 0.2 mU/L v 0.9 and 0.3 to 2.5 mU/L, respectively), related to a loss of the usual nocturnal increase in TSH pulse amplitude, but not of TSH pulse frequency. In the eucorticoid state, there was an increase of mean 24-hour TSH to 1.3 +/- 0.8 mU/L (P < .001) under normalization of the mean 24-hour TSH pulse amplitude. The nocturnal TSH surge also increased (median, 0.21; range, 0.15 to 0.4 mU/L) under restoration of the usual nocturnal increase in TSH pulse amplitude. In conclusion, Cushing's syndrome is associated with a decrease of mean 24-hour plasma TSH, related to a decrease of TSH pulse amplitude (not of TSH pulse frequency). The nocturnal TSH surge is decreased in Cushing's syndrome associated with a loss of the usual nocturnal increase of TSH pulse amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile thyrotropin and prolactin secretion in a patient with a mixed thyrotropin- and prolactin-secreting pituitary adenoma.

The circadian and pulsatile thyrotropin (TSH) and prolactin (PRL) release was investigated in a patient with slight hyperthyroidism due to a mixed TSH- and PRL-secreting pituitary adenoma. Blood was withdrawn every 10 min for 24 h (before and after medical treatment); pulse characteristics were analyzed by Desade and Cluster programs (values as mean +/- SD). The inappropriately high mean 24-h TSH concentration of 3.55 +/- 0.31 mU/l was associated with a higher mean 24-h TSH pulse amplitude but unaltered mean 24-h TSH pulse frequency relative to healthy controls. The nocturnal TSH surge (absolute surge 0.5 mU/l, relative surge 16%) was low, related to a loss of the usual nocturnal increase of TSH pulse amplitude and TSH pulse frequency. Chronic treatment with octreotide resulted in a modest clinical and biochemical improvement of the hyperthyroid state; addition of bromocriptine at a later stage had no further beneficial effect. At the end of the follow-up period the mean 24-h TSH paradoxically had increased to 5.33 +/- 0.81 mU/l. The nocturnal TSH surge also increased (absolute surge 1.9 mU/l, relative surge 42%), but circadian changes in TSH pulsatility remained absent. In the untreated period the increased mean 24-h PRL concentration of 234 +/- 24 micrograms/l was associated with an increased mean 24-h PRL amplitude, whereas the 24-h PRL pulse frequency (N = 4) was lower relative to controls. No circadian PRL rhythm was present. After octreotide and bromocriptine treatment the mean 24-h PRL concentration and mean 24-h PRL pulse amplitude were unchanged, but a clear nocturnal increase of PRL now was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile thyrotropin secretion in nonthyroidal illness.

Pulsatile and nocturnal TSH secretion was investigated in 16 healthy controls (group A) and 21 patients with nonthyroidal illness (NTI; group B). Ten patients had normal plasma T3 and T4 values (group B1), and 11 patients had decreased plasma T3 with normal or low plasma T4 (group B2). Mean 24-h TSH secretion in NTI patients was higher than that in controls (3.1 +/- 0.7 vs. 1.7 +/- 0.7 mU/L; P < 0.01; mean +/- SD). This was associated with an increased TSH pulse amplitude in NTI patients relative to controls [Desade, 0.79 +/- 0.46 vs. 0.44 +/- 0.20 mU/L (P < 0.01); Cluster, 0.64 +/- 0.42 vs. 0.39 +/- 0.20 mU/L (P < 0.05)]. There was no difference in TSH pulse amplitude between subgroups B1 and B2. TSH pulse frequency was not different between NTI patients and controls (approximately 10 pulses/24 h). The mean 24-h TSH concentration was significantly related to the mean 24-h TSH pulse amplitude but not to the mean 24-h TSH pulse frequency. The absolute nocturnal TSH surge in NTI patients was lower than that in controls (0.6 +/- 0.6 vs. 1.0 +/- 0.6 mU/L; P < 0.05). The lower nocturnal TSH surge in patients with decreased plasma T3 (group B2) was associated with a loss of the usual nocturnal increase of TSH pulse amplitude; the usual nocturnal increase in TSH pulse frequency was preserved. This was also observed in the six patients (two in group B1 and four in group B2) in whom the nocturnal TSH surge was completely absent. The changes in nocturnal TSH secretion in NTI resemble those found in central hypothyroidism, suggesting that features of central hypothyroidism are involved in the euthyroid sick syndrome.

Pulsatile thyrotropin release in patients with untreated pituitary disease.

Pulsatile and nocturnal TSH secretion was investigated in 16 healthy controls (group A) and 19 patients with untreated pituitary disease [7 were euthyroid without suprasellar extension (group B), 6 were euthyroid with suprasellar extension (group C) of pituitary lesions, and 6 were hypothyroid with or without suprasellar extension (group D)]. Pulse analysis was performed using Desade and Cluster algorithms. No changes were observed among groups A-D in mean 24-h TSH pulse amplitude [values given as mean +/- SD; Desade, 0.4 +/- 0.2 vs. 0.7 +/- 0.4 vs. 0.6 +/- 0.4 vs. 0.5 +/- 0.2 mU/L (P = NS); Cluster, 0.4 +/- 0.2 vs. 0.7 +/- 0.4 vs. 0.5 +/- 0.3 vs. 0.4 +/- 0.2 mU/L (P = NS)] or in the mean 24-h TSH pulse frequency (approximately 10 pulses/24 h). The mean 24-h TSH concentration was highly correlated to the mean 24-h TSH pulse amplitude in controls (r = 0.93; P < 0.001) and patients (r = 0.63; P < 0.01), but not to the mean 24-h TSH pulse frequency. The nocturnal TSH surge was similar in controls and euthyroid patients without suprasellar extension (group A, 1.0 +/- 0.6; group B, 1.3 +/- 1.3 mU/L; P = NS), but was decreased in euthyroid patients with suprasellar extension (group C, 0.3 +/- 1.0 mU/L; P < 0.05) and hypothyroid patients (group D, 0.4 +/- 0.4 mU/L; P < 0.05). The decreased nocturnal TSH surge was associated with a loss of the usual nocturnal increase in TSH pulse amplitude, whereas the usual nocturnal increase in TSH pulse frequency was maintained. In conclusion, 1) mean 24-h TSH pulse amplitude and frequency are unchanged in untreated patients with pituitary disease; and 2) patients with central hypothyroidism as well as euthyroid patients with suprasellar extension of pituitary lesions had a decreased nocturnal TSH surge associated with a loss of the usual nocturnal increase in TSH amplitude, but not TSH pulse frequency.

Hypothyroid-like regulation of the pituitary-thyroid axis in stable human immunodeficiency virus infection.

Thyroid function and regulation were studied in 14 consecutive male outpatients with asymptomatic human immunodeficiency virus (HIV) infection (CDC II/III, n = 8) or AIDS (CDC IV, n = 6) who were free of concomitant infections and hepatic dysfunction, and in eight healthy, age- and weight-matched male controls. Blood was sampled every 10 minutes over 24 hours for measurement of thyrotropin (TSH). Thereafter, thyroid hormones and TSH responsiveness to thyrotropin-releasing hormone (TRH) were measured. Triiodothyronine (T3) and thyroxine (T4) did not differ between HIV-infected patients and controls, but HIV patients had lower thyroid hormone-binding index ([THBI] HIV patients, 1.01 +/- 0.02; controls, 1.11 +/- 0.03; P < .02), free thyroxine (FT4) index (94 +/- 3 v 110 +/- 4, P < .01), FT4 (11.8 +/- 0.4 v 14.3 +/- 0.4 pmol/L, P < .01), and reverse triiodothyronine (rT3) values (0.18 +/- 0.01 v 0.26 +/- 0.02 nmol/L, P < .001) and higher thyroxine-binding globulin ([TBG] 20 +/- 1 v 16 +/- 1 mg/L, P < .02) values. Mean 24-hour TSH levels were increased in HIV patients (2.39 +/- 0.33 v 1.44 +/- 0.16 mU/L, P < .05), associated with increased mean TSH pulse amplitude and TSH responsiveness to TRH. No differences were observed between asymptomatic HIV-seropositive and AIDS patients. In conclusion, there is a hypothyroid-like regulation of the pituitary-thyroid axis in stable HIV infection, which differs distinctly from the euthyroid sick syndrome in non-HIV-nonthyroidal illnesses.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian changes in pulsatile TSH release in primary hypothyroidism.

OBJECTIVE: We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism. DESIGN: In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured. SUBJECTS: Nine patients with overt primary hypothyroidism, seven patients with subclinical hypothyroidism and 16 healthy controls. MEASUREMENTS: Computer-assisted analysis by the Desade and Cluster programs. RESULTS: Both computer-assisted programs revealed an increased TSH pulse amplitude in both overt and subclinical hypothyroidism versus controls (Desade: 36.9 +/- 31.4 (mean +/- SD) (P < 0.001) and 2.8 +/- 1.9 (P < 0.001) vs 0.4 +/- 0.2 mU/l; Cluster: 25.6 +/- 25.1 (P < 0.001) and 2.4 +/- 1.4 (P < 0.001) vs 0.4 +/- 0.2 mU/l). TSH pulse frequency remained unchanged with approximately 10 pulses/24 hours. A highly significant correlation was found between the mean 24-hour TSH concentration and the TSH pulse amplitude in all controls and patients but not to TSH pulse frequency. The nocturnal TSH surge was absent in six out of nine patients with overt primary hypothyroidism. The deficient nocturnal rise of TSH in primary hypothyroidism vs controls (22 +/- 51 vs 82 +/- 41%, P < 0.001), was associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency. CONCLUSIONS: Mean 24-hour TSH pulse amplitude is increased in primary hypothyroidism, but TSH pulse frequency remains unchanged. The decrease of the nocturnal TSH increase in primary hypothyroidism is associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency.

The nocturnal thyroid-stimulating hormone surge is absent in overt, present in mild primary and equivocal in central hypothyroidism.

UNLABELLED: The nocturnal TSH surge was studied in controls, in 34 patients with hypothalamic/pituitary disease and in 21 patients with primary hypothyroidism. It was absent in 5/12 hypothyroid patients and in 5/22 euthyroid patients with hypothalamic/pituitary disease (42% vs 23%, NS). Central hypothyroidism relative to euthyroidism was associated with a lower absolute (0.3 +/- 0.4 vs 0.9 +/- 1.0 mU/l, p less than 0.05) and relative (24 +/- 31 vs 63 +/- 51%, p less than 0.05) nocturnal rise in TSH. In primary hypothyroidism, the nocturnal TSH surge was absent in eight of ten patients with overt, in one of five patients with mild and in none of six patients with subclinical hypothyroidism. The relative nocturnal rise in TSH was normal in mild (54 +/- 33%) and subclinical (92 +/- 69%), but decreased in overt hypothyroidism (2 +/- 10%). Plasma T4 was positively and 09.00 plasma TSH negatively related to the relative nocturnal TSH surge in primary hypothyroidism, but not in central lesions. In both conditions, however, a positive relationship was observed between the relative nocturnal TSH surge and the relative increase of TSH to TRH. IN CONCLUSION: (a) The nocturnal TSH surge is usually absent in overt hypothyroidism but present in mild primary hypothyroidism and equivocal in central hypothyroidism. This limits its usefulness as an adjunct in the diagnosis of central hypothyroidism. (b) The magnitude of the nocturnal TSH surge in patients with hypothalamic/pituitary disease or primary hypothyroidism is directly related to the TSH response to TRH, and thus appears to be determined by the directly releasable TSH pool of the pituitary.

Pulsatile secretion of thyrotropin during fasting: a decrease of thyrotropin pulse amplitude.

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every 10 min during 24 h for measurement of TSH by a sensitive immunoradiometric assay. Fasting induced a decrease in plasma T3 [1.73 +/- 0.06 vs. 1.36 +/- 0.04 nmol/L; P less than 0.01 (mean +/- SE), control period vs. fasting] and thyroglobulin (52 +/- 8 vs. 35 +/- 7 pmol/L; P less than 0.001) and an increase in plasma rT3 (0.30 +/- 0.06 vs. 0.44 +/- 0.09 nmol/L; P less than 0.02). Plasma T4, thyroid hormone binding index, and free T4 were not statistically different in both periods. The mean plasma 24-h TSH concentration was lower during fasting than in the control period (2.0 +/- 0.3 vs. 1.0 +/- 0.2 mU/L; P less than 0.005). This was associated with a decrease in mean TSH pulse amplitude during fasting (Desade program: 0.6 +/- 0.1 vs. 0.3 +/- 0.1 mU/L; P less than 0.01; Cluster program: 0.5 +/- 0.1 vs. 0.2 +/- 0.1 mU/L; P less than 0.05), whereas TSH pulse frequency during fasting was unchanged (Desade program: 8.4 +/- 0.9 vs. 9.8 +/- 0.8 pulses/24 h; Cluster program: 9.5 +/- 0.5 vs. 7.9 +/- 0.9 pulses/24 h). There was a highly significant correlation between the mean 24-h TSH concentration and the mean TSH pulse amplitude during both the control period and fasting. Although the decrease in TSH concentration during fasting was evident over 24 h, fasting especially decreased the absolute (1.3 +/- 0.3 vs. 0.4 +/- 0.1 mU/L, P less than 0.02) and the relative (101 +/- 18% vs. 40 +/- 14%; P less than 0.02) nocturnal TSH surge (mean TSH 0000-0400 h vs. mean TSH 1500-1900 h). The decreased nocturnal TSH surge during fasting was associated with a significantly decreased TSH pulse amplitude, but with an unaltered number of TSH pulses between 2000-0400 h. In conclusion, fasting decreases 24-h TSH secretion and the nocturnal TSH surge in the absence of a change in plasma T4 concentration. This is associated with a decreased TSH pulse amplitude, whereas TSH pulse frequency remains unchanged.