Lipid profile and response to statin therapy in patients with hypopituitarism

ABSTRACT Objective: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. Subjects and methods: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. Results: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. Conclusions: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

Hormona de crecimiento en sangre de papel filtro para el diagnóstico de deficiencia de hormona de crecimiento / Growth hormone of dried blood spot for the diagnosis of growth hormone deficiency

INTRODUCCIÓN: El diagnóstico de deficiencia de hormona de crecimiento (DHC) es difícil de establecer, y se puede asociar a serias complicaciones, especialmente en el período neonatal. La prueba de estímulo de secreción de hormona de crecimiento (HC) se considera de elección para el diagnóstico, pero presenta complicaciones metodológicas y se asocia a efectos adversos. Los neonatos presentan aumento de la secreción de HC de forma fisiológica, siendo una ventana diagnóstica. OBJETIVO: Evaluar si la muestra de sangre en papel filtro tomada en el período neonatal, en contexto del tamizaje neonatal de hipotiroidismo congénito y fenilcetonuria, permite diferenciar pacientes con DHC, de los que no la presentan. PACIENTES Y MÉTODO: Estudio de casos y controles mediante determinación de concentración de HC en sangre de papel filtro extraída en período neonatal, comparando controles con DHC con casos con deficiencia descartada. Se realizó extracción de la muestra del papel filtro, obteniendo dos discos de 0,125 pulgada por cada uno de los pacientes desde el centro de la mancha de sangre del papel, para un ELISA de HC humana altamente sensible basado en el uso de anticuerpos policlonales dirigidos contra la HC humana recombinante de 22kDa de peso molecular. RESULTADOS: Se obtuvo un total de 7 casos de DHC y 10 controles. La mediana de concentración de HC de papel filtro en los casos es 2,0 ng/ml (Rango intercuartil 3,6 ng/ml) y controles 2,05 ng/mL (RIC 2,0 ng/ml), U de Mann-Withney 30,5 (p = 0,68). Los dos casos con deficiencia de hormonas hipofisarias múltiples (DHHM) presentan concentraciones menores a 1 ng/ml. CONCLUSIÓN: La muestra de papel filtro no permitió diferenciar a los pacientes con DHC de los casos controles, aunque los casos con DHHM presentaron concentraciones mucho menores, en comparación a la deficiencia de hormona de crecimiento aislada (DHCA).

INTRODUCTION: The diagnosis of growth hormone deficiency (GHD) is difficult to determine, and could be associated with severe complications, especially in the neonatal period. The stimulation test of growth hormone (GH) secretion is considered the gold standard for diagnosis, but it has methodological complications and is associated with adverse effects. Neonates present physiological increased secretion of GH, representing a diagnostic window. OBJECTIVE: To evaluate if the dried blood spot on filter paper obtained in the neonatal period, as part of a neonatal screening for con genital hypothyroidism and phenylketonuria, allows differentiating patients with GHD from those who do not have it. PATIENTS AND METHOD: Study of cases and controls by measuring the GH concen tration in dried blood spot on filter paper obtained in the neonatal period, comparing controls with GHD with cases with discarded deficiency. The sample was extracted from the filter paper, obtaining two 0.125 inch discs per each patient from the center of the blood spot on the paper, for a highly sen sitive ELISA assay for human GH based on the use of polyclonal antibodies against 22 kDa recom binant human GH. RESULTS: Seven cases of GHD and ten controls were obtained. The median GH concentration of the dried blood spot in the cases is 2.0 ng/ml (Interquartile range 3.6 ng/ml) and 2.05 ng/ml (Interquartile range 2.0 ng/ml) in the controls, Mann-Whitney U test 30.5 (p = 0.68). The two cases with multiple pituitary-hormone deficiency (MPHD) present concentrations lower than 1 ng/ml. CONCLUSION: The dried blood spot sample did not differentiate GHD patients from control cases, although MPHD cases present much lower concentrations compared to isolated growth hor mone deficiency (IGHD).

Síndrome de QT largo y taquicardia ventricular en torsade de pointes secundarios a hipopituitarismo: una asociación a tener en cuenta: caso clínico / Long QT syndrome and polymorphic ventricular tachycardia due to hypopituitarism: report of one case

Symptoms of hypopituitarism are usually chronic and nonspecific, but rarely the disease can have acute and life threatening manifestations. We report a 53 years old female with a pituitary adenoma that was admitted to our hospital because of syncope. The electrocardiogram showed sinus bradycardia with a prolonged QT interval. Frequent runs of non-sustained polymorphic ventricular tachycardia were noted on telemetry. The patient had a history of severe acute headaches in the previous days and laboratory tests revealed severe secondary hypothyroidism, adrenal insufficiency and a decrease in pituitary hormones. A magnetic resonance imaging of the head showed changes in the size and contrast enhancement of the adenoma. A diagnosis of hypopituitarism secondary to pituitary apoplexy was made and treatment with hydrocortisone and, subsequently, levothyroxine was started. Hormonal disorders such as hypothyroidism, adrenal insufficiency or hypopituitarism should be considered as unusual causes for reversible cardiomyopathy, long QT syndrome and ventricular arrhythmias.

Síndrome de Cornelia de Lange y deficiencias hormonales pituitáricas múltiples, una asociación inusual: Caso clínico / Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association: Clinical case

El síndrome de Cornelia de Lange es una enfermedad genética caracterizada por rasgos faciales distintivos, falla de medro, microcefalia y varias malformaciones asociadas. Sus principales alteraciones endocrinológicas son las anomalías genitales. Se presenta un adolescente de 13 años, tratado por neumonía aspirativa complicada y que presentaba el fenotipo del síndrome de Cornelia de Lange, que incluía retraso global del desarrollo, trastorno de succión-deglución, talla baja y alteración del desarrollo sexual. Su edad ósea era muy retrasada, por lo que se realizó un estudio endocrinológico completo. Se le diagnosticaron hipotiroidismo central, deficiencia de la hormona de crecimiento y deficiencia de hormona luteotrópica y folículoestimulante, compatibles con el diagnóstico de deficiencias hormonales pituitáricas múltiples. Tuvo cortisol basal, hormona adrenocorticotrópica y prolactina normales. Recibió suplencia hormonal tiroidea. Es inusual la asociación de este síndrome con deficiencias hormonales pituitáricas múltiples. Se sugiere la evaluación de los distintos ejes endócrinos en estos pacientes.

Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Indicaciones actuales para el uso de la hormona de crecimiento / Growth hormone treatment update

La baja talla en la infancia es una causa frecuente de derivación al endocrinólogo infantil, y corresponde la mayoría de las veces a variantes normales del crecimiento. Inicialmente la terapéutica con hormona de crecimiento humana estaba circunscripta a los niños que presentaban deficiencia de dicha hormona. A partir de la producción de la hormona recombinante humana por ingeniería genética se pudo ampliar su uso a otras patologías.

Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

Colestasis neonatal e hipoglucemia como forma de presentación de hipopituitarismo congénito / Neonatal cholestasis and hypoglycemia like form of congenital hypopituitarism presentation

El hipopituitarismo congénito es una enfermedad poco frecuente, de clínica variable. La hipoglucemia neonatal es una de las formas habituales de presentación; la colestasis es un síntoma raro de esta enfermedad. Se presenta el caso de un lactante de 2 meses hospitalizado por ictericia colestática. Agregó episodios reiterados de hipoglucemia grave. Se investigaron causas metabólicas y endocrinológicas. Se arribó a la etiología a través de la obtención de una muestra crítica que demostró el déficit de hormonas contrarreguladoras. Se completó el diagnóstico de hipopituitarismo congénito con la demostración del déficit de hormona tiroidea y hormona de crecimiento. Se confirmó el defecto neuroanatómico de "síndrome de sección del tallo hipofisario", determinado por agenesia del tallo pituitario, hipoplasia hipofisaria y neurohipófisis ectópica. Se inició tratamiento hormonal restitutivo, con una buena respuesta y una buena evolución posterior.

Congenital hypopituitarism is a rare disease, of variable clinic. The neonatal hypoglycemia is one of the habitual forms of presentation; the cholestasis is a rare symptom of this disease. This is the case of a 2-months-old infant hospitalized for cholestatic jaundice. He added repeated episodes of severe hypoglycemia. We investigated metabolic and endocrine causes. The etiology was clarified by obtaining a critical sample that demonstrated the counterregulatory hormone deficiency. The diagnosis of congenital hypopituitarism was completed withconfirmation of thyroid hormone and growth hormone deficiencies. It was confirmed the neuro-anatomical defect of "syndrome of pituitary stalk section" determined by pituitary stalkagenesis, pituitary hipoplasia, and ectopic neurohypophysis. Hormone replacement therapy was started with good response and outcome.

Sheehan's syndrome with central diabetes insipidus / Síndrome de Sheehan e diabetes insípido central

Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

A síndrome de Sheehan está relacionada à ocorrência de hipopituitarismo pós-parto, geralmente precedido por hemorragia pós-parto. Essa condição clínica ainda constitui causa comum do hipopituitarismo observado em países em desenvolvimento como a Índia. Essa síndrome se caracteriza pela insuficiência da glândula hipofisária anterior, porém com a conservação das funções da glândula hipofisária posterior. A disfunção da hipófise posterior, sob a forma de diabetes insipidus central, é algo raramente observado em pacientes que apresentam a síndrome de Sheehan. Neste artigo, descrevemos o caso de uma jovem que, após o sexto parto, apresentou hemorragia pós-parto grave, seguida pela evolução de pan-hipopituitarismo que foi confirmado por pesquisa hormonal e exames de imagem que evidenciaram sela vazia. A jovem também apresentou poliúria. Os resultados do teste de privação de água e exame de resposta à vasopressina indicaram diabetes insípido central. A paciente fazia uso contínuo de desmopressina para controlar a poliúria.

A Case of Sheehan's Syndrome that Manifested as Bilateral Ptosis

Hypothyroidism can cause a variety of signs and symptoms of the neuromuscular system. However, ptosis in a patient with hypothyroidism is very rare. We report here on a case of central hypothyroidism that was due to Sheehan's syndrome and it manifested as bilateral ptosis in a 51-yr-old woman. She complained of exertional dyspnea and weakness. About 25-yr ago, she had a history of severe postpartum vaginal bleeding. The laboratory studies demonstrated hypopituitarism with secondary hypothyroidism. The ptosis was improved by replacement of thyroid hormone. Hypothyroidism should be considered in the differential diagnosis of patients who manifest with ptosis and that prompt replacement of hormone can lead to a complete recovery.

Congenital hypopituitarism: Monitoring after coronary artery bypass grafting.

Cardiovascular disease in patients with congenital hypopituitarism is not rare; however, there is a lack of reports referring to cardiac interventions in such patients. We present a 76-year-old man with complete pituitary hormone deficiency, who presented with recurrent events of unstable angina. He had a significant stenosis of the left anterior descending artery and he underwent off-pump coronary artery bypass. Our aim is to present the successful management of this patient with congenital hypopituitarism who underwent cardiac surgery and to review the relevant literature.

Hiponatremia grave como manifestación inicial de síndrome de Sheehan de diagnóstico tardío: caso clínico / Hyponatremia secondary to panhypopituirarism: report of one case

Hyponatremia is common among older people and its possible causes are not thoroughly investigated in this age group. We report a 69 years old female with a history of hypothyroidism in treatment that consulted for malaise, anorexia and a severe hyponatremia that required hospital admission. A new interrogation, revealed that the patient suffered an uterine hemorrhage in 1977, remaining with agalactia. She also referred asthenia since 1990. Her serum cortisol was below normal limits and a sella turcica magnetic resonance imaging revealed a pituitary atrophy. The patient was treated with cortisol and discharged in good conditions.

Hiponatremia sintomática como forma de presentación clínica de un macroadenoma hipofisiario: Comunicación de tres casos / Hyponatremia associated to pituitary adenomas: Report of three patients

Severe hyponatremia occurring as the presenting feature of hypopituitarism secondary to pituitary adenomas is rare. We report three patients with this condition: Two elderly males (74 and 78 year-old) presenting with impaired consciousness and low plasma sodium after an episode of diarrhea and a 56-year-old male presenting with impaired consciousness after an episode of vomiting. All had clinical features of hypopituitarism and pituitary adenomas were found on imaging studies. Two were subjected to a trans sphenoidal resection of the adenoma.

Anormalidades metabólicas en la deficiencia de la hormona de crecimiento / Metabolic Abnormalities in growth hormone deficiency

Increased cardiovascular morbidity and mortality has been reported in adult subjects with growth hormone deficiency (GHD). Long term follow up of a large cohort of patients with adult onset GHD, suggests that GH therapy may contribute to a reduced risk of nonfatal stroke, particularly in women and in a decline in nonfatal cardiac events in GHD men(1,2). Adult hypopituitary patients with untreated growth hormone deficiency have been shown to have a cluster of cardiovascular risk factors such as increased visceral adiposity, disturbances in lipoprotein metabolism, premature atherosclerosis, impaired fibrinolytic activity, increased peripheral insulin resistance, abnormal cardiac structure, impaired cardiac performance and endothelial dysfunction (3,4). Several of these risk factors have now been confirmed in double blind, randomized, placebo controlled trials (5,6). Metabolic changes in GH deficient children and adolescents have been evaluated only quite recently and superficially. In this article we will discuss these metabolic abnormalities and their underlying mechanism in untreated GHD subjects and we will review the beneficial effect of growth hormone therapy in adults, adolescents and children with GHD.

Se ha reportado un aumento en la morbilidad y mortalidad de pacientes adultos con deficiencia de la hormona de crecimiento (DHC). El seguimiento a largo plazo de una cohorte de pacientes con DHC sugiere que la administracion de hormona de crecimiento puede contribuir a una reducción en el número de los accidentes cerebrovasculares no fatales, particularmente en mujeres y de eventos cardíacos en hombres(1,2). Pacientes adultos con hipopituitarismo y una DHC cursan con un acúmulo de factores de riesgo cardiovascular tales como un aumento en la adiposidad visceral, alteraciones en el metabolismo lipoproteico, ateroesclerosis prematura, actividad fibrinolítica alterada, resistencia a la insulina, masa y función cardíaca alterada y disfunción endotelial (3,4). Varios de estos factores de riesgo han sido comprobados en estudios doble ciego, randomizados con placebo (5,6). Las alteraciones metabólicas en niños y adolescentes deficientes de hormona de crecimiento han sido evaluadas sólo recientemente y de manera aún superficial. En este manuscrito discutiremos estas anormalidades y los mecanismos etilógicos subyacentes en sujetos DHC no tratados y revisaremos el efecto beneficioso de la terapia con hormona de crecimiento en niños, adolescentes y adultos.

Cardiac tamponade as a presenting manifestation of Sheehan syndrome.

We report a 38-year-old Syrian woman who presented with progressive breathlessness, hypotension and circulatory collapse. Echocardiogram revealed a large pericardial effusion with evidence of cardiac tamponade. There was a history of secondary amenorrhoea, loss of axillary and pubic hair following childbirth at 28 years of age. Investigations revealed low levels of gonadotrophins, oestrogen, prolactin and thyrotrophin but normal levels of basal and post-synacthen (ACTH) cortisol. An MRI of the sella showed atrophic changes of the pituitary. She was treated with intravenous fluids, dopamine infusion, intravenous hydrocortisone and thyroxine replacement. The clinical suspicion of Sheehan syndrome facilitated early administration of corticosteroids, adequate thyroxine replacement and rapid resolution of pericardial effusion.

Colangitis esclerosante primaria en paciente con panhipopituitarismo autoinmune: presentación de 1 caso / Primary sclerosing cholangitis in a patient with autoimmune panhypopituitarism: a case report

Se presentó un paciente con diagnóstico de un panhipopituitarismo autoinmune (diabetes insípida vasopresinsensible, hiperprolactinemia, hipotiroidismo, hipogonadismo secundario e insuficiencia corticosuprarrenal) establecido hace 3 años, que a finales del año 2005 comenzó a presentar dolor intenso en epigastrio e hipocondrio derecho, acompañado de vómitos con restos de alimentos, fiebre elevada con escalofríos, seguido de coluria, acolia e íctero verdínico, hepatomegalia, elevación importante de la bilirrubina, la fosfatasa alcalina leucocitaria y la gamma glutamil transpectidasa, leucocitosis, que requirió tratamiento con antibióticos por vía endovenosa y simuló, al inicio, los diagnósticos de litiasis coledociana, tumor de cabeza de páncreas y hepatitis colangiolítica por fármacos. Estos episodios se fueron repitiendo cada vez con más frecuencia, hasta llegarse al diagnóstico de colangitis esclerosante primaria por colangiopancreatografía retrógrada endoscópica y biopsia hepática. Se revisó la literatura, pero no se encontraron reportes de la asociación de colangitis esclerosante primaria con panhipopituitarismo autoinmune.

A case of a patient with diagnosis of autoimmune panhypopituitarism (vasopressinsensitivity diabetes insipidus, hyperprolactinemia, hypothyroidism, secondary hypogonadism and corticosuprarenal insufficiency) established 3 years ago, was reported. At the end of 2005, he began to present an acute pain in the epigastrium and right hypochondrium, accompanied with vomiting with food residual, high fever with chills, followed of choluria, acholia and greenish icterus, hepatomegaly, marked elevation of bilirubin, leukocyte alkaline phosphatase and gamma glutamil transpeptidase, leukocytosis, that required treatment with antibiotics by endovenous route and mimmicked, at the beginning, the diagnoses of choledocian lithiasis, pancreatic head tumor, and cholangiolitic hepatitis caused by drugs. These episodes were frequently repeated until the diagnosis of primary sclerosing cholangitis was made by retrograde endoscopic cholangiopancreatography and liver biopsy. Literature was reviewed, but no reports of association of primary sclerosing cholangitis with autoimmune panhypopituitarism were found.

Delayed Puberty due to Pituitary Stalk Dysgenesis and Ectopic Neurohypophysis

Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was referred to our clinic because of the absence of the development of secondary sexual characteristics. The patient had no complaints of physical discomfort. Random serum testosterone and luteinizing hormone level were obtained and found to be low. The combined pituitary function stimulation test revealed a partial hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and showed decreased pituitary stalk enhancement and ectopic neurohypophysis. Therefore, we conclude that the delayed puberty was a result of hypopituitarism due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was started on hormone replacement therapy and gradually developed secondary sexual characteristics.