Posterior Pituitary Insufficiency Research Articles

Approach to the Patient: A Case With an Unusual Cause of Hypopituitarism.

Hypopituitarism, which refers to insufficiency of one or more hormones of the pituitary, can be due to myriad causes. The clinical and radiological spectrum of the condition is heterogeneous, based on the patient's age, gender, clinical setting, and/or other past medical history. Hypopituitarism includes central hypocortisolism, hypothyroidism, hypogonadism, and growth hormone deficiency. Both hypo- and hyperprolactinemia can be associated with hypopituitarism, with low prolactin signifying more extensive pituitary damage. Posterior pituitary insufficiency (arginine vasopressin deficiency) occurs either in isolation or with anterior pituitary hormone deficiency. Clinical symptomatology of hypopituitarism is usually nonspecific and insidious in onset and progression. Overall, the most common cause of hypopituitarism is a pituitary adenoma and/or its management (surgery, radiotherapy, pharmacotherapy, or a combination of these). However, it is this subset of patients which is more likely to be identified and managed in a timely manner, possibly alleviating the premature mortality associated with hypopituitarism. What is more challenging is the recognition of hypopituitarism in less common settings, which may be either due to direct involvement of the pituitary (infection, traumatic brain injury, or infiltrative causes) or indirectly as a consequence of the primary process (thalassemia, vasculotoxic snakebite, subarachnoid hemorrhage). These entities are often under-recognized, and increased awareness can help in greater recognition of the burden. Further, pituitary insufficiency in most of these settings is dynamic and may progress, or rarely, show recovery of function. This renders complexity to the problem, but makes it even more imperative to suspect, screen, and appropriately manage patients with less common causes of hypopituitarism.

Pituitary Metastasis Presenting With Central Diabetes Insipidus and Panhypopituitarism

Abstract Background: Metastatic involvement of the pituitary gland and infundibular stalk is rare, accounting for about 2% of all diagnosed pituitary masses. Although primary tumors from almost every organ have been reported, breast and lung cancers are the most common primary tumors to metastasize to the pituitary gland. The clinical presentation varies and can include headache, visual impairment, diabetes insipidus, and panhypopituitarism. The posterior lobe of the pituitary is more susceptible to metastatic involvement than the anterior lobe due to its direct blood supply from the systemic circulation, whereas the anterior lobe is supplied by the hypophyseal portal system. Additionally, the smaller posterior lobe can be destroyed with less metastatic volume, allowing for earlier manifestation of symptoms. Clinical Case: An 81-year-old woman with a history of Stage IIA ER+ IDC of the left breast status post lumpectomy and axillary lymph node dissection in 1999 followed by mastectomy in 2009 due to local recurrence presented with confusion for two weeks. At the time, she had known lung metastases and was on palliative chemotherapy. CT head showed a 1.8 cm and 2.3 cm calvarial lytic lesion in the right occipital bone and at the vertex, respectively. MRI brain/pituitary revealed a well-circumscribed, enhancing suprasellar mass measuring 9 x 10 mm likely involving the pituitary infundibulum and hypothalamus with mass effect on the optic chiasm. Laboratory results were consistent with secondary adrenal insufficiency, central hypothyroidism, and hypogonadotropic hypogonadism. Prolactin was mildly elevated due to stalk effect. The patient also had hypernatremia and inappropriately low urine osmolality, which nearly tripled after administration of desmopressin, confirming central diabetes insipidus. She was subsequently started on hydrocortisone, levothyroxine, and desmopressin. Laboratory Results: Prolactin 30.47 (reference range 4.79-23.3 mIU/mL), IGF-1 88 (17-193 ng/mL), 7am ACTH 3.4 (7.2-63.3 pg/mL), 7am cortisol 0.6 (6.2-29 µg/dL), TSH 3.03 (0.47-6.9 U/L), FT4 0.351 (0.75-2 ng/dL), FSH 0.2 (25.8-134.8 mIU/mL), LH <0.1 (7.7-58.5 mIU/mL), estradiol <5 (5-138 pg/mL); before desmopressin: Na 154 (reference range 135-145 mEq/L), urine osm 162 (50-1,200 mOsm/kg); after desmopressin: Na 143 (reference range 135-145 mEq/L), urine osm 469 (50-1,200 mOsm/kg) Conclusion: While pituitary metastases remain rare, their prevalence is expected to increase due to more sensitive biochemical tests and imaging techniques coupled with advances in cancer therapy that help patients with metastatic disease live longer. Interesting in our case is the patient’s age, which is significantly older than the median age reported in the literature, and her presentation with total anterior and posterior pituitary insufficiency after a prolonged oncologic course marked by progression of disease.

Acute and Chronic Posterior Pituitary Insufficiency Among Traumatic Brain Injury Patients at a Tertiary Care Center

Abstract Background: Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Disorders of salt and water balance are the most commonly recognized medical complications in the immediate post-TBI period and contribute to early morbidity and mortality. Objective: We aimed to evaluate the prevalence of acute (during hospital stay) and chronic posterior pituitary dysfunction in patients of head injury admitted at our tertiary care hospital. Study Design: Prospective, Observational study. Participants: 136 patients, attending tertiary care in North India with TBI with radiological evidence of head injury. Methodology: The severity of brain injury was assessed by the Glasgow Coma Scale (GCS), and Modified Rankin Scale (MRS) score at the time of admission. Lab measurements, apart from routine CBC and biochemical tests, included tests of serum and urinary osmolality, serum sodium, cortisol, and thyroid function test during the hospital stay. All patients were monitored closely during the hospital stay. Surviving patients were evaluated at 3, 6, and 12 months of follow-up. Urinary output and water deprivation tests were done to determine chronic posterior pituitary dysfunction. The results were compared against normative data obtained from 25 matched, healthy controls. Serum & urinary osmolality was measure by the freezing point method. Diabetes insipidus (DI) and Syndrome of inappropriate ADH secretion (SIADH) were diagnosed according to standard criteria. Results: Of 136 patients admitted, 61 (44.85%) had a mild head injury (GCS, ≤8), 47 (35.55%) had a moderate injury (GCS, 9-12), and 27 (19.85%) had a severe injury (GCS, 13-15). DI occurred in 10 patients (7.4%), while SIADH was observed in 4 patients in the immediate TBI period. Risk factors for diabetes insipidus were GCS of ≤ 8 at admission, midline shift, and surgical intervention. DI was an independent risk factor for death. There was a negative correlation between the presence of DI and GCS score (r, -0.367). Most of the patients with DI (8 out of 10) died during the hospital stay. One patient persisted to have partial diabetes insipidus and another one SIADH at three months post-TBI; both patients had recovered at six months of follow-up. No new case of DI or SIADH occurred on the follow up to 12 months. Conclusion: The incidence of acute DI in severe head injury (GCS ≤ 8) could be an indicator of the severity of TBI, and associated with increased mortality as most of our patients died during the hospital stay.

Endonasal endoscopic transsphenoidal resection of intrinsic third ventricular craniopharyngioma: surgical results.

Intrinsic third ventricular craniopharyngiomas (IVCs) have been reported by some authors to "pose the greatest surgical challenge" of all craniopharyngiomas (CPAs). A variety of open microsurgical approaches have historically been used for resection of these tumors. Despite increased utilization of the endoscopic endonasal approach (EEA) for resection of CPAs in recent years, many authors continue to recommend against use of the EEA for resection of IVCs. In this paper, the authors present the largest series to date utilizing the EEA to remove IVCs. The authors reviewed a prospectively acquired database of the EEA for resection of IVCs over 14 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital. Preoperative MR images were examined independently by two neurosurgeons and a neuroradiologist to identify IVCs. Pre- and postoperative endocrinological, ophthalmological, radiographic, and other morbidities were determined from retrospective chart review and volumetric radiographic analysis. Between January 2006 and August 2017, 10 patients (4 men, 6 women) ranging in age from 26 to 67 years old, underwent resection of an IVC utilizing the EEA. Preoperative endocrinopathy was present in 70% and visual deterioration in 60%. Gross-total resection (GTR) was achieved in 9 (90%) of 10 patients, with achievement of near-total (98%) resection in the remaining patient. Pathology was papillary in 30%. Closure incorporated a "gasket-seal" technique with nasoseptal flap coverage and either lumbar drainage (9 patients) or a ventricular drain (1 patient). Postoperatively, complete anterior and posterior pituitary insufficiency was present in 90% and 70% of patients, respectively. In 4 patients with normal vision prior to surgery, 3 had stable vision following tumor resection. One patient noted a new, incongruous, left inferior homonymous quadrantanopsia postoperatively. In the 6 patients who presented with compromised vision, 2 reported stable vision following surgery. Each of the remaining 4 patients noted significant improvement in vision after tumor resection, with complete restoration of normal vision in 1 patient. Aside from the single case (10%) of visual deterioration referenced above, there were no instances of postoperative neurological decline. Postoperative CSF leakage occurred in 1 morbidly obese patient who required reoperation for revision of closure. After a mean follow-up of 46.8 months (range 4-131 months), tumor recurrence was observed in 2 patients (20%), one of whom was treated with radiation and the other with chemotherapy. Both of these patients had previously undergone GTR of the IVC. The 10 patients described in this report represent the largest number of patients with IVC treated using EEA for resection to date. EEA for resection of IVC is a safe and efficacious operative strategy that should be considered a surgical option in the treatment of this challenging subset of tumors.

Diabetes Insipidus after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI.

Neurological, psychiatric, ophthalmological, and endocrine complications in giant male prolactinomas: An observational study in Algerian population.

Introduction:Prolactinomas are less frequent, but more invasive in males. Giant ones (≥4 cm) are extremely rare in literature. Their neurological, psychiatric and endocrine complications are life threatening. Our aim was to report the largest mono center series in order to analyze their frequency, their characteristics, and their complications.Subjects and Methods:All patients had clinical examination, hormonal, ophthalmological, and radiological assessment based on computed tomography scan and cerebral magnetic resonance imaging. Positive diagnosis was based on clinical symptoms, high prolactin ± immunohistochemy study. Mixed adenomas were excluded by hormonal exploration and immunohistochemy. For those who received medical treatment only, a reduction in tumor size was considered a supplementary positive point for the diagnosis.Results:Among 154 male prolactinomas seen between 1987 and 2013, we observed 44 giant tumors (28.5%). Median age = 36 years, and 38.3% were under 30. Median tumor height = 53.95 mm (40–130) and median prolactin = 15,715 ng/ml (n < 20). Solid and cystic aspect ± calcifications was observed in 25%. 42 had cavernous sinuses invasion. Other invasions were: Posterior= 65.9%, anterior= 63.6%, temporal= 15.9% and frontal = 9%. For endocrine complications: Hypogonadism = 98.4%, thyrotroph and corticotroph deficits were seen in respectively 34%, and 32%. Posterior pituitary insufficiency was observed in one case. For ophthalmological complications: Optic atrophy = 46%, Ptosis = 6.8%, diplopia/strabismus = 4.5%. Neurological complications were: Memory loss and/or unconsciousness = 18.2%, epilepsy = 15.9%, frontal syndrome = 9% and obstructive hydrocephalus = 6.8%.Conclusion:Giant prolactinomas account for 28% in our population. Severe neurological complications are frequent. But, obstructive hydrocephalus is rare, which argues for a slow progression.

Lymphocytic hypophysitis in the pediatric population

Lymphocytic hypophysitis (LYH) is a rare inflammatory disease of the pituitary gland that usually affects women in their ante- or immediate postpartum period; males are affected less frequently than females. An autoimmune pathogenesis is suggested. Symptoms comprise anterior and/or posterior pituitary insufficiency of varying degrees. So far, specific characteristics of this rare disease in childhood are not well described. We report the case of a 12-year-and-11-month-old boy with histologically confirmed LYH clinically presenting with diabetes insipidus. A high-dose steroid therapy was administered, in which the therapeutic effect was uncertain. His 6-year follow-up is presented. The literature is reviewed for children presenting with LYH; their characteristics, pituitary involvement, and clinical follow-up are listed and discussed. Even though magnetic resonance imaging can be highly suspicious for LYH, only surgical exploration can confirm the diagnosis. The efficacy of medical treatment is still controversial; a close follow-up is necessary to control and correct the endocrinological function, if required.

Hypophysitis superimposed on a non-functioning pituitary adenoma: Diagnostic clinical, endocrine, and radiologic features

Pituitary adenomas are common neoplasms requiring medical and/or surgical treatment when associated with hormonal hypersecretion. Treatment of non-functioning pituitary adenomas is necessary when symptoms of mass effect or hormonal deficits occur. However, therapeutic options, including surgical resection and/or radiotherapy, can be associated with significant complications. Hence, it is important to consider disorders that could present in a similar manner to pituitary adenomas, for which surgery is not the indicated therapeutic approach. We describe herein a 38-yr-old woman who presented with a pituitary lesion that was considered to be a non-functioning pituitary adenoma. Due to lack of hormonal deficits and/or compression of adjacent structures, we opted for conservative management and followup with consecutive magnetic resonance imaging. Fifteen months after initial diagnosis, considerable enlargement of the lesion was noted, extending mainly superiorly and indenting the optic chiasm. Repeated endocrine investigation revealed partial anterior pituitary insufficiency. The patient underwent trans-sphenoidal resection of the pituitary lesion; histology revealed a null cell pituitary adenoma and lymphocytic hypophysitis (LYH) of the non-neoplastic adenohypophysial gland. Post-operatively, complete anterior and partial posterior pituitary insufficiency developed. This case illustrates the effects of new-onset LYH in a patient with a pre-existing non-functioning pituitary adenoma. Being aware of this rare possibility is important, as enlargement of the pituitary lesion may not be caused by expansion of the preexisting tumor, but by the onset of LYH of the nonneoplastic pituitary tissue.

Pituitary diseases in pregnancy

Pituitary adenomas are the most common pituitary disorder affecting pregnancy, and prolactinomas are the most common of the hormone-secreting pituitary adenomas. Hyperprolactinemia must be corrected to allow ovulation and fertility. Bromocriptine has been shown to be safe for use during early gestation. There is less than a 2% risk of microprolactinoma enlargement during pregnancy but a greater than 15% risk of symptomatic enlargement of a macroprolactinoma. Treatment options for patients with macroadenomas include stopping bromocriptine when pregnancy is diagnosed and reinstituting with tumor enlargement, continuous bromocriptine throughout pregnancy, and prepregnancy tumor debulking by surgery. The diagnosis of acromegaly may be difficult to make during pregnancy and relies, in part, on the persistence of the normal pulsatile secretion of growth hormone and loss of this secretory characteristic with a tumor. The growth hormone oversecretion may exacerbate tendencies to gestational diabetes, fluid retention, and hypertension. Treatment for acromegaly and other tumors generally may be deferred until after delivery. There are rare reports of enlargement of clinically nonfunctioning and growth hormone secreting tumors during pregnancy, and surveillance is needed. Tumors may need to be differentiated from lymphocytic hypophysitis. Patients with chronic hypopituitarism usually will need treatment with gonadotropins or pulsatile GnRH to become pregnant and may need increased steroid coverage during labor and delivery. Hypopituitarism developing during pregnancy is usually caused by lymphocytic hypophysitis and usually also will require steroid replacement therapy. Hypopituitarism arising postpartum may be caused by either lymphocytic hypophysitis or Sheehan's syndrome, and the latter may present as an acute or chronic syndrome. Borderline diabetes insipidus may manifest during pregnancy because of increased vasopressin degradation caused by markedly increased levels of placental vasopressinase. Treatment with desmopressin usually is satisfactory. Patients presenting with either anterior or posterior pituitary insufficiency in the peripartum period should always be evaluated for function of the other portion of the pituitary.

SUBNORMAL GROWTH HORMONE (GH) LEVELS WITH NORMAL GROWTH

4 children with a pituitary or hypothalamic tumor were studied. 3 of them underwent surgery, post-operatively a growth-spurt followed by normal growth as observed. One of these patients showed an excessive weight gain. The fourth patient in whom the tumor was not removed had a normal growth rate as well. In all 4 patients endocrine evaluation revealed varying degrees of anterior and posterior pituitary insufficiency. Peak CH levels following various stimuli were extremely low in all patients. Prolactin activity in serum as measured by a local pigeon crop assay was elevated in one patient only. In all patients the serum activity of somatomedin was determined by bioassay, serum levels of insulin were measured by RIA during stimulation tests. Our findings suggest that a biological substance other than GH might have induced somatomedin generation in these patients. Supported by Deutsche Forschungsgemeinschaft, SFB 34

Sulfation factor (somatomedin): an explanation for continued growth in the absence of immunoassayable growth hormone in patients with hypothalamic tumors.

Three children with hypothalamic tumors were found to have varying degrees of anterior and posterior pituitary insufficiency. Two had undetectable plasma levels of immunoreactive growth hormone (less than 1 ng/ml) and one had levels within the normal fasting range (1–4 ng/ml). None responded to any stimulus with a rise in plasma immunoreactive growth hormone. In spite of this, all patients showed normal or accelerated linear growth and markedly excessive weight gain. Sulfation factor activity (somatomedin) was detectable in the serum of all three patients. This indicates that some substance other than immunoreactive growth hormone, capable of producing growth and stimulating formation of sulfation factor is being produced in these children and is responsible for this syndrome.

Endocrinopathy associated with pineal tumor.

The diagnosis of tumor of the pineal seems eminently likely when the following clinical picture is present: the patient is a male in his late teens or early twenties who gives clinical and laboratory evidence of combined anterior and posterior pituitary insufficiency; his skull X ray shows calcification in the pineal region, and air study identifies a mass lesion deforming the third ventricular shadow, with or without evidence of internal hydrocephalus. On the basis of the case histories of 5 patients studied by the authors as well as 11 case histories abstracted from the literature, we have concluded that this clinical picture, which often develops before the onset of central nervous system or ophthalmologic symptoms or signs, may occur more commonly than has previously been recognized. The recognition of tumor of the pineal at an early stage, when only the endocrine, and not its other, more ominous manifestations are present, would seem to carry important implications for prognosis and therapy.

Adrenal steroid inhibition of vasopressin release from the neurohypophysis of normal subjects and patients with Addison's disease.

There is a large body of evidence to indicate that adrenal steroids decrease distal renal tubular reabsorption of water. A popular view is that this effect may be due to antagonism of the action of vasopressin on the renal tubules (1), but others (2) have postulated that corticoids may exert a direct effect on permeability of the renal tubular cells to water. Recent studies in patients with combined anterior and posterior pituitary insufficiency (3) suggested that adrenal steroids increase free water excretion by suppressing release of vasopressin from hypothalamic portions of the neurohypophysis. Further investigation of this preliminary hypothesis in normal subjects and in patients with Addison's disease forms the basis of this report.'

Sheehan's syndrome with diabetes insipidus

A case of Sheehan's syndrome and diabetes insipidus of simultaneous onset is described. The insufficiency of the posterior lobe of the pituitary is proved by the absence of normal physiologic response to the administration of nicotine and intravenously administered hypertonic saline solution. The literature concerning postpartum anterior pituitary insufficiency associated with posterior pituitary insufficiency is reviewed.