Disorder of hypothalamic-pituitary-gonadal axis induced by abusing of anabolic-androgenic steroids for short time: A case report.

The aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis functionality on a bodybuilding competitioner before, during and after the use of anabolic-androgenic steroids. A young healthy man was followed up for 4 months. The subject reported his drug administration protocol through periodic interviews and performed laboratory tests to monitor the function of his hypothalamic-pituitary-gonadal axis. Time 1 (before the steroids use) shows all hormones levels (follicle-stimulating hormone = 4,2 mUI/ml, luteinising hormone = 3,7 mUI/ml and total testosterone = 5,7 ng/ml) within reference values. In Time 2, after 8 weeks on steroids abuse, a complete hypothalamic-pituitary-gonadal axis derangement is evident with noticeable negative feedback (follicle-stimulating hormone = 1,47 mUI/ml, luteinising hormone = 0,1 mUI/ml and total testosterone = 1,47 ng/ml). At the third moment (40 days after Time 2), we can see a tendency to recovery, however, the serum levels of the investigated hormones were still considerably lower than the baseline values. At the end, we could conclude that the use of anabolic-androgenic steroids, at supraphysiological dosages, even for a short time (8 weeks), causes severe disorder in the hypothalamic-pituitary-gonadal axis. The endogenous testosterone synthesis was severely compromised by important decline in serum luteinising hormone levels.

Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period / Reavaliação da dosagem sérica do fator de crescimento insulina-símile-1 (IGF-1) para o diagnóstico da deficiência isolada e combinada de hormônio de crescimento no período de transição

OBJECTIVE: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. SUBJECTS AND METHODS: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). RESULTS: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. CONCLUSION: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

OBJETIVO: Avaliar a acurácia da dosagem sérica de IGF-1 no diagnóstico da deficiência de hormônio de crescimento isolada (DGHI) ou combinada (DGHC) na fase de transição. SUJEITOS E MÉTODOS: Quarenta e nove pacientes com DGH na infância [16 DGHI (10 homens) e 33 DGHC (24 homens); idade 23,2 ± 3,5 anos] realizaram teste de tolerância à insulina (TTI), com pico de GH < 5 µg/L considerado diagnóstico de DGH na transição. Função hipofisária e níveis de IGF-1 foram determinados na amostra basal do TTI e os pacientes foram reclassificados em GH suficientes (SGH; n = 12), DGHI (n = 7) ou DGHC (n = 30). RESULTADOS: Cinco (31%) pacientes com DGHI e 32 (97%) com DGHC na infância persistiram com DGH no reteste. Um paciente com DGHI foi reclassificado como DGHC e três com DGHC como DGHI. Os picos médios de GH foram 0,2 ± 0,3 µg/L (DGHC), 1,3 ± 1,5 µg/L (DGHI) e 18,1 ± 13,1 µg/L (SGH). O nível médio de IGF-1 foi maior no grupo SGH (272 ± 107 ng/mL) comparado com DGHI (100,2 ± 110) e DGHC (48,7 ± 32,8) (p < 0,01). IGF-1 baixo foi observado em todos os pacientes reclassificados como DGHC, 86% dos DGHI e 8,3% dos SGH, resultando em sensibilidade de 97,3% e especificidade de 91,6% para detecção de DGH na transição; valor de corte de 110 ng/mL mostrou 94,5% sensibilidade e 100% especificidade. O nível médio de IGF-1 foi similar nos pacientes com DGHI ou DGHC com uma, duas, três ou quatro deficiências hipofisárias associadas. CONCLUSÃO: A dosagem sérica de IGF-1 mostrou-se acurada para substituir o TTI na detecção tanto de DGHI como DGHC na transição.

Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period.

OBJECTIVE: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. SUBJECTS AND METHODS: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). RESULTS: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. CONCLUSION: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

Glucagon stimulation test for the diagnosis of GH deficiency in adults.

The insulin tolerance test (ITT) is considered the test of choice for the diagnosis of GH deficiency (GHD). However, in patients with contraindications to ITT, alternative provocative tests must be used with appropriate cut-offs. The glucagon stimulation test has proved to be a safe, low-cost and effective means of stimulating GH secretion, and therefore can be considered as a suitable alternative to the ITT. We have studied the GH response to the glucagon test in 33 patients with known pituitary disease, 12 males and 21 females, aged between 21 and 60 yr (41.18 +/- 9.47 yr); 5 had isolated GHD and 28 had panhypopituitarism. We also evaluated a control group of 25 individuals, matched for age and sex (8 males and 17 females), aged between 20 and 60 yr (39.28 +/- 12.10 yr). They were selected via the ITT if their peak GH response was > 5.0 ng/ml. GH peak after glucagon was significantly lower in the group of patients compared to the control group (0.49 +/- 0.85 vs 8.69 +/- 5.85 ng/ml, p = 0.0001). Receiver-operating characteristic (ROC) plot analyses of the control and GHD group showed an area under the curve of 0.982 for GH peak response to glucagon. The response value of 3.0 ng/ml showed the best pair of sensitivity (97%)/specificity (88%), and was chosen as the cut-off defining GHD. After evaluation of positive predictive values (PPV) and negative predictive values (NPV) through simulation of different prevalences of the disease, we concluded that the cut-off point of 3.00 ng/ml maximizes both PPV and NPV (100%). In conclusion, we have shown that the glucagon stimulation test has a good performance and great diagnostic accuracy for the diagnosis of GHD.

Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan.

OBJECTIVE: Growth hormone deficiency (GHD) is associated with adverse changes in lipid profile. However, changes in lipids through life in a homogeneous group of GHD subjects have not been defined. PATIENTS AND MEASUREMENTS: We examined lipid levels in a group of untreated severely GHD patients with a mutation in the GHRH receptor gene from a rural community in North-east Brazil. Lipid profiles in 15 GHD subjects [eight children and adolescents (one male), age (median [range]) 13.2 (5.4-19.9) years; seven adults (one male), age 47 (33-66) years] were compared with those in 29 indigenous controls from the same extended kindred [17 children and adolescents (six male), age 10.2 (5.3-18.4) years; 12 adults (eight male), age 54.5 (33-80) years]. All GHD subjects had a peak GH response of < 0.5 ng/ml in response to an insulin tolerance test and extremely reduced IGF-1 levels (median 5.5 ng/ml). Data were compared between cohorts and with an age- and sex-matched white American reference population. RESULTS: Abnormalities were confined to plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. More GHD children had levels of plasma TC and LDL-C above the 95th percentile for our reference population (3/8 and 4/7, respectively) compared to controls (0/17 and 1/15, respectively) (P < 0.05). In the adults, median TC and LDL-C levels were higher in the GHD than controls (P < 0.05) (6.3 vs. 4.1 mmol/l; 4.4 vs. 2.7 mmol/l, respectively). Median Z-scores, calculated using values from the reference population, were not different between GHD children and adults for both TC (+0.8 vs.+0.4) and LDL-C (+1.4 vs.+0.7). CONCLUSIONS: The lipid profile in children as well as in adults with very severe GHD is adversely modified. There would appear to be no significant worsening of the lipid abnormality with duration of GHD or achievement of adulthood.

Evaluation of free insulin-like growth factor-I measurement on the diagnosis and follow-up treatment of growth hormone-deficient adult patients.

OBJECTIVE: Insulin-like growth factor (IGF-I) and IGF binding protein-3 (IGFBP-3) are GH-dependent and their concentrations have been used in the diagnosis of GH deficiency. Recently, the free fraction of IGF-I has received more attention. The aim of the study was to assess the role of free IGF-I in the diagnosis of GH deficiency in adults, and in follow-up during treatment with recombinant human GH (rhGH). DESIGN AND PATIENTS: We studied 24 adult patients with pituitary disease and GH deficiency and 25 matched controls. Nine patients were re-evaluated after 6 months of treatment with rhGH (0.25 U/kg/week). MEASUREMENTS: Serum levels of IGF-I, free IGF-I, IGFBP-3 and IGFBP-1 were measured by immunoradiometric assay. RESULTS: Serum free IGF-I levels were significantly lower in the GH deficient group than in the normal group (mean: 0.84 and 1.32 micrograms/l respectively, P = 0.0009). Furthermore, serum IGF-I levels were also lower (mean: 92.24 and 230.47 micrograms/l respectively, P < 0.0001). 63% of patients had serum IGF-I concentration below the normal range. For free IGF-I, 52% of the GH deficient patients showed levels below the lowest value obtained for the normal group. Seventy-five percent of the patients showed at least one of the two determinations below the normal range. The free-total IGF-I ratio was significantly higher (P = 0.025) in GH deficient group (range: 0.19-21.29, mean: 2.53) than in normal controls (range: 0.2-2.15, mean: 0.6). Regarding IGFBP-3 and IGFBP-1 no differences were observed between the two groups. During rhGH treatment the increase in serum total and free IGF-I and IGFBP-3 paralleled the beneficial effects on body composition. CONCLUSIONS: Free IGF-I may be another useful method for the diagnosis of GH deficiency, particularly if related to total IGF-I concentration.

Central hypothyroidism resulting from pituitary suppression and peripheral thyrotoxicosis in a premature infant born to a mother with Graves disease.

We observed the sequential changes in serum thyroid hormones and thyroid-stimulating hormone receptor antibodies in an infant born at 30 weeks of gestation to a mother with florid Graves disease. Transient central hypothyroidism caused by pituitary suppression was observed after the resolution of peripheral thyrotoxicosis induced by thyroid-stimulating antibody. Central hypothyroidism became overt when the suppression of the pituitary gland after fetal thyrotoxicosis was combined with weak activity of thyroid-stimulating antibody after birth.

[Hypothalamo-hypophyseal amenorrhea. I. The clinical and laboratory manifestations]. / Amenorrea hipotálamo-hipofisaria. I. Manifestaciones clínicas y de laboratorio.

This study included 15 women 18-36 years old with primary or secondary amenorrhea, low FSH and LH, a negative response to clormadinone and serum prolactin (Prl) levels less than 20.0 ng/ml. The following tests were performed on alternate days: LH and FSH determinations every 20 minutes (pulses) during 2-4 hours (n = 15); LH and FSH response to a single dose of GnRH 100 micrograms IV (n = 15) and after administration of 100 micrograms IM of GnRH daily during four consecutive days (n = 7); TRH test 200 micrograms IV (n = 9); oral metoclopramide-Prl induced response (10 mg) (n = 2); one to three basal determinations of cortisol, estradiol (E2), T3, T4, and TSH (n = 15). All patients had serum E2 levels less than 10.0 pg/ml and none showed a regular LH or FSH pulsatility. In seven patients (group A) serum LH had a 10-30 fold increase above basal levels in response to GnRH, while the other eight patients (group B) showed no response at all; serum FSH changes were most irregular in both group. In group A no other hormonal deficiencies were detected, while in group B only three patients had an isolated LH-FSH deficiency, and in the other five this deficiency was accompanied by Prl, TSH, and/or ACTH lack. The present results suggest that: 1) group A represents isolated GnRH deficiency and the amenorrhea has hypothalamic etiology; 2) group B had LH-FSH deficiency of pituitary origin, in most cases associated to other pituitary hormone deficiencies; 3) the lack of LH response to an initial single dose of GnRH is not an absolute indicator of hypophyseal amenorrhea.

A familial syndrome of isolated "aplasia" of the anterior pituitary. Diagnostic studies and treatment in the neonatal period.

A male newborn infant developed hypoglycemia, collapsed, and convulsed at eight hours of age. The diagnosis of pituitary "aplasia" was suspected, because of a previously affected female sibling, and treatment with glucocorticoids was instituted. Diagnostic studies revealed a deficiency of thyrotropin, growth hormone, and prolactin. He is now six months of age and is thriving on replacement therapy. Analysis of previous reports of this entity indicates that isolated "aplasia" of the anterior pituitary is a genetic syndrome with an autosomal recessive mode of transmission. The course in this patient suggests that this disorder, if diagnosed, is amenable to therapy.