Giant Prolactinoma Causing Hydrocephalus and Intracranial Hypertension as First Manifestations of Multiple Endocrine Neoplasia Type 1.

Context: Overall, giant prolactinomas are rare tumors (4%), especially those larger than 60 mm (1%). Despite the predominance of macroadenoma documented in multiple endocrine neoplasia type 1 (MEN1)-related prolactinoma, only three giant prolactinoma cases were described so far (size > 40 mm and prolactin > 1,000 ng/mL). None of them was larger than 60 mm or presented hydrocephalus or intracranial hypertension (ICH) as initial manifestation of MEN1. Case Description: A 21-years-old man presented with ICH as the first clinical manifestation of MEN1. He harbored a MEN1 germline mutation but refused periodic vigilance after normal hormonal screening at age 14 years. During investigation, magnetic resonance imaging (MRI) of the skull showed an expansive sellar/parasellar lesion (75 × 44 × 36 mm) with moderate to severe supratentorial obstructive hydrocephalus and an extremely high serum prolactin (PRL) of 10,800 ng/mL, without combined hypersecretion of other pituitary hormones. He was diagnosed with giant prolactinoma, and cabergoline was initiated. The patient evolved with early improvement of clinical complaints for hydrocephalus and ICH and PRL reached normal values (11 ng/mL) in association with significant tumoral shrinkage after 18 months on cabergoline. After 2 months of cabergoline, cerebrospinal fluid leakage was diagnosed and corrective surgery was provided. The mean dose of cabergoline was 3 mg/week throughout treatment. Conclusion: We reported the first case with hydrocephalus and ICH as the initial clinical manifestation of a giant prolactinoma in MEN1. From our knowledge, this is the largest MEN1-related prolactinoma reported so far. Notably, all four MEN1-related giant prolactinomas cases reported were younger than 21 years strengthening the importance to routine MEN1 genetic testing for prolactinoma in this age group. Also, they all had initial effective response with dopamine agonist ensuring this drug as first-line treatment for MEN1-related giant prolactinoma. However, the scarce number of treated patients and progression of cabergoline resistance in two of them suggest strict surveillance.

Diagnosis of subclinical central hypothyroidism in patients with hypothalamic-pituitary disease by Doppler echocardiography.

OBJECTIVE: The diagnosis of subclinical central hypothyroidism in hypothalamic-pituitary patients cannot be established by serum markers of thyroid hormone action. Myocardial function by echocardiography has been shown to reflect thyroid hormone action in primary thyroid dysfunction. We evaluated the performance of echocardiography in diagnosing subclinical central hypothyroidism. DESIGN: Cross-sectional and before and after. METHODS: Echocardiography and serum thyroid hormones were assessed in overt primary (n=20) and central (n=10) hypothyroidism, subclinical primary hypothyroidism (n=10), hypothalamic-pituitary disease with normal free thyroxine (FT(4); n=25), and controls (n=28). Receiver operating characteristic (ROC) curves were generated using overt hypothyroidism patients and selected cut-off values were applied to detect both primary and central subclinical hypothyroidism. After levothyroxine (l-T(4)) intervention, patients were echocardiographically reevaluated at predefined targets: normal thyrotropin (TSH) in primary hypothyroidism, normal FT(4) in overt central hypothyroidism, and higher than pretreatment FT(4) in echo-defined subclinical central hypothyroidism. RESULTS: Parameters with highest areas under the ROC curves (area under the curve (AUC) ≥0.94) were as follows: isovolumic contraction time (ICT), ICT/ejection time (ET), and myocardial performance index. Highest diagnostic accuracy (93%) was obtained when at least one parameter was increased (positive and negative predictive values: 93%). Hypothyroidism was echocardiographically diagnosed in eight of ten patients with subclinical primary hypothyroidism and in 14 of 25 patients (56%) with hypothalamic-pituitary disease and normal serum FT(4). Echocardiographic abnormalities improved significantly after l-T(4) and correlated (0.05

Urinary calcium excretion and insulin resistance in patients with acromegaly.

BACKGROUND: Renal complications in acromegaly include glomerular hyperfiltration, insulin resistance, hypercalciuria and urolithiasis. The aim of this study was to investigate whether urinary calcium (U(Ca)) excretion is a direct consequence of growth hormone secretion or secondary to hyperfiltration and/or insulin resistance. METHODS: We performed a cross-sectional study of 58 patients diagnosed with acromegaly. Demographic data were obtained, serum analysis was performed, including insulin-like growth factor (IGF)-1, and 24-h urine collection, to measure urinary protein excretion, U(Ca) and phosphate excretion, as well as fractional excretion of sodium and potassium. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Patients were predominantly male (60.3%), and their mean age was 45.9 ± 14 years. Hypercalciuria was present in 24% of patients. Patients with higher HOMA-IR had higher IGF-1 levels, a trend toward higher body mass index and higher U(Ca) excretion. In univariate analysis, U(Ca) excretion was associated with HOMA-IR (r = 0.472, P = 0.001), phosphaturia (r = 0.457, P = 0.001), IGF-1 (r = 0.398, P = 0.002) and creatinine clearance (r = 0.394, P = 0.001). HOMA-IR and phosphaturia were independently associated with U(Ca) excretion. No independent associations were found between phosphaturia and HOMA-IR or IGF-1. CONCLUSIONS: The present study revealed an association between hypercalciuria and insulin resistance in patients with acromegaly. Further studies are required to fully understand the pathogenesis of these abnormalities in patients with acromegaly.

Influência dos níveis séricos de IGF-I e de testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos / Influence of serum IGF-I and testosterone on lipid and glycemic profile in acromegalic men

OBJETIVOS: Investigar a influência do IGF-I e testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos. MÉTODOS: Foram avaliados 15 homens acromegálicos. RESULTADOS: Os pacientes hipogonádicos apresentaram HDL-c mais baixo e triglicérides, LDL-c, glicemia, GH e IGF-I mais elevados. Os valores de IGF-I correlacionaram-se inversamente com HDL-c (r = - 0,57, p = 0,04) e diretamente com triglicerídeos (r = 0,62, p = 0,01) e glicemia (r = 0,66, p = 0,008), enquanto a testosterona correlacionou-se diretamente com HDL-c (r = 0,52, p = 0,05) e inversamente com triglicerídeos (r = - 0,57, p = 0,02); LDL (r = - 0,53, p = 0,04) e glicemia (r = - 0,54, p = 0,03). O IGF-I e a testosterona correlacionaram-se inversamente (r = - 0,585, p = 0,028). CONCLUSÃO: Estes resultados sugerem que a intervenção mais importante na redução do risco cardiovascular nesses pacientes é o controle da atividade da doença.

OBJECTIVES: To evaluate the influence of IGF-I and testosterone on the lipid profile and glycemia in acromegalic men. METHODS: Fifteen acromegalic men were studied. RESULTS: The hypogonadic patients presented lower HDL-c and higher tryglicerides, LDL-c, glycemia, GH and IGF-I. Serum IGF-I was inversely correlated with HDL-c (r = - 0.57, p = 0.04) and directly with TG (r = 0.62, p = 0.01) and glycemia (r = 0.66, p = 0.008), whereas serum testosterone correlated directly with HDL-c (r = 0.52, p = 0.05) and inversely with TG (r = - 0.57, p = 0.02), LDL-c (r = - 0.53, p = 0.04) and fasting blood glucose (r = - 0.54, p = 0.03). IGF-I and testosterone were inversely correlated (r = - 0.585, p = 0.028). CONCLUSION: These results suggest that the most important intervention in reducing cardiovascular risk in these patients is to control the activity of the disease.

[Influence of serum IGF-I and testosterone on lipid and glycemic profile in acromegalic men]. / Influência dos níveis séricos de IGF-I e de testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos.

OBJECTIVES: To evaluate the influence of IGF-I and testosterone on the lipid profile and glycemia in acromegalic men. METHODS: Fifteen acromegalic men were studied. RESULTS: The hypogonadic patients presented lower HDL-c and higher tryglicerides, LDL-c, glycemia, GH and IGF-I. Serum IGF-I was inversely correlated with HDL-c (r = - 0.57, p = 0.04) and directly with TG (r = 0.62, p = 0.01) and glycemia (r = 0.66, p = 0.008), whereas serum testosterone correlated directly with HDL-c (r = 0.52, p = 0.05) and inversely with TG (r = - 0.57, p = 0.02), LDL-c (r = - 0.53, p = 0.04) and fasting blood glucose (r = - 0.54, p = 0.03). IGF-I and testosterone were inversely correlated (r = - 0.585, p = 0.028). CONCLUSION: These results suggest that the most important intervention in reducing cardiovascular risk in these patients is to control the activity of the disease.

[hGH treatment impact on adrenal and thyroid functions]. / Impacto do tratamento com GH sobre as funções tireoidiana e adrenal.

Somatotrophic status is a major determinant of both thyrotrophic and corticotrophic axis. In growth hormone deficient patients, somatotrophic replacement increases the conversion rate of the inactive form of the thyroid hormone (T4) to its active form (T3), whereas the same replacement induces the conversion of cortisol, which is hormonally active, in cortisone, its inactive form. This review details the effects of GH on these two hormonal axis, possible mechanisms and clinical implications for the management of hypopituitary patients.

Impacto do tratamento com GH sobre as funções tireoidiana e adrenal: [revisão] / hGH treatment impact on adrenal and thyroid functions: [review]

O estado somatotrófico é modulador importante dos eixos tirotrófico e corticotrófico. Enquanto a reposição somatotrófica em pacientes com deficiência de GH aumenta a conversão do hormônio inativo (T4) na sua forma ativa (T3), aumentando dessa forma a ação biológica do hormônio tireoidiano, a mesma reposição induz no eixo corticotrófico a conversão de cortisol, hormonalmente ativo, em cortisona, que é biologicamente inativa. Nessa revisão, foram discutidos os efeitos do GH nesses dois eixos hormonais, os possíveis mecanismos e as implicações clínicas no manejo dos pacientes com hipopituitarismo.

Somatotrophic status is a major determinant of both thyrotrophic and corticotrophic axis. In growth hormone deficient patients, somatotrophic replacement increases the conversion rate of the inactive form of the thyroid hormone (T4) to its active form (T3), whereas the same replacement induces the conversion of cortisol, which is hormonally active, in cortisone, its inactive form. This review details the effects of GH on these two hormonal axis, possible mechanisms and clinical implications for the management of hypopituitary patients.

Growth hormone replacement improves thyroxine biological effects: implications for management of central hypothyroidism.

CONTEXT: The biological significance of GH-induced changes in serum TH concentrations is unknown. It has been suggested that serum free T(4) (FT(4)) should be targeted at the high-normal range during GH replacement. OBJECTIVE: Our objective was to evaluate the effects of GH replacement on T(4) biological effects. HYPOTHESIS: If GH modulates thyroxine biological effects, serum FT(4) should be targeted accordingly. DESIGN AND SETTING: We conducted observational (study 1) and interventional (studies 2 and 3)/outpatient studies. PATIENTS: Thirty-two GH-deficient patients (13 off GH; 22 on l-T(4)) participated in the study. INTERVENTIONS: In study 2, levothyroxine was administered to increase FT(4) (>1.0 ng/dl). In study 3, GH was administered or withdrawn. MAIN OUTCOME MEASURES: We measured FT(4), total T(3) (TT(3)), myocardial isovolumic contraction time (ICT), and resting energy expenditure (REE). RESULTS: In study 1, off-GH and on-GH groups had similar FT(4), but off GH showed lower TT(3) (P < 0.01) and REE (P = 0.02), higher ICT (P < 0.05) than on-GH and controls. On GH, ICT and REE correlated only with TT(3) (r = -0.48; r = 0.58; P < 0.05). Off GH, ICT correlated only with FT(4) (P < 0.01). In study 2, off GH, levothyroxine intervention increased FT(4) (P = 0.005) and TT(3) (P = 0.012), decreased ICT (P = 0.006), and increased REE (P = 0.013); ICT and FT(4) changes correlated (r = -0.72; P = 0.06). On GH, levothyroxine increased FT(4) (P = 0.0002), TT(3) (P = 0.014), and REE (P = 0.10) and decreased ICT (P = 0.049); REE and TT(3) changes correlated (r = 0.60; P = 0.05). In study 3, GH decreased FT(4), increased TT(3), decreased ICT, and increased REE (P < 0.05). REE correlated (P < 0.05) with IGF-I (r = 0.57) and TT(3) (r = 0.64). ICT correlated only with TT(3) (r = -0.46). CONCLUSIONS: GH replacement improves the biological effects of T(4). Serum FT(4) should be targeted at the high-normal range in GH-deficient patients only off GH replacement.