In this study, we present data regarding spectrum of hypopituitarism for which data from India is scant. The most common cause for hypopituitarism is sellar/suprasellar tumors which is consistent with the prevalent data. Bates et al
] reported tumors in 89% of their hypopituitarism series which is similar to that seen in our series. However, etiology has been more diverse in our series.
Chatterjee et al
. have described the largest published series of adult hypopituitarism (82 cases) till date in India.[17
] Hence, present study is the largest series of adult hypopituitarism (91 cases). They noted pituitary adenoma in 37.8%, Sheehan's syndrome in 27%, snake bite in 14.6%, suprasellar lesion in 7.3%, and empty sella in 7.3%. Lower incidence of Sheehan's syndrome in our study may be due to availability of free obstetrical care to our population at service hospitals and better socioeconomic strata of our sample population. The high incidence of snake bite could be due to geographical variations in snake bite pattern. They found hypocortisolism in 81.7%, hypothyroidism in 63.4%, hypogonadism in 78%, and GHD in 64.6% of their patients. This study is in contrast to our observations.
A study among non-Cushing's pituitary macroadenoma from India observed hypothyroidism, hypoadrenalism, and hypogonadism in 24%, 54%, and 52% of patients, respectively, at initial presentation but a significant proportion of them went onto recover their pituitary functions after intervention.[6
] However, a majority of them were evaluated before receiving radiotherapy and also had a short follow-up period. In contrast, the incidence of hypothyroidism, hypoadrenalism, and hypogonadism was 87%, 72%, and 100%, respectively, in present series. Radiotherapy was administered to 53% of these patients and most of them were on long-term follow-up and these could explain the high incidence of hypopituitarism.
From India, another study studied incidence of hypopituitarism in patients who had received cranial irradiation for extrasellar tumors.[5
] The author showed that pituitary dysfunction was common in these patients. However, in our study, we did not come across any case of hypopituitarism due to cranial irradiation for extrasellar tumors. This suggests that hypopituitarism after radiotherapy for extrasellar tumors are often missed as cases are under follow-up at oncology center and do not come to attention for non-specific symptoms due to hypopituitarism. Though recommendations for evaluation of pituitary function following cranial radiation exist,[18
] it is not often followed.
We came across a case of hypopituitarism due to snake bite. It has been estimated that 2 00 000 people are bitten by venomous snake (viperidae family is a major contributor) in India every year.[19
] Clinicians treating snake bites from tropical countries like ours need to be aware of this entity and these patients should be under long-term follow-up to document any pituitary insufficiency. The presentation can be acute like apoplexy or chronic as seen in our patient who was diagnosed two years after the event. Only a handful cases have been reported from India till date.[17
Another common cause in the developing countries is Sheehan's syndrome. There have been few case series of this entity from India.[3
] Patients can have a varied spectrum of pituitary dysfunction in Sheehan syndrome from panhypopituitarism to isolated hormone deficiency and from acute presentation to a chronic form. In their seminal work, Zargar et al
] described the clinical profile of Sheehan's syndrome. They reported 149 patients with Sheehan's syndrome and estimated total cases of this entity to be 38 691 in Kashmir valley. They documented one, two, three, four, and five pituitary hormone deficiencies in 17.4%, 23.5%, 18.8%, 17.4%, and 22.8%, respectively. We diagnosed six cases of Sheehan's syndrome and all had panhypopituitarism. Hypogonadism and hypoadrenalism were universal and hypothyroidism was present in four. None of them had diabetes insipidus. All had chronic form and MRI showed empty sella in all.
Pituitary abscess is another rare cause of hypopituitarism. We previously reported one case of recurrent pituitary abscess[13
] with panhypopituitarism. The pus from the abscess of this patient was sterile and no cause could be ascertained in him. Dutta et al
] reported four cases of pituitary abscess and all had presented with systemic manifestations in addition to endocrine dysfunction. Our patient did not have any systemic symptoms. In the largest series of pituitary abscess published till date, the authors report that abscess can be successfully treated but the accompanying hypopituitarism is usually irreversible.[26
Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are being more frequently reported as etiology of hypopituitarism.[27
] The incidence of traumatic brain injuries is 150/100 000 in India.[28
] Post-traumatic hypopituitarism is observed in about 5.4 to 40% of patients with a history of TBI usually presenting as an isolated deficiency in most cases.[29
] Hypopituitarism has been observed in 19% of patients with ischemic stroke and 47% of patients with SAH, presenting as an isolated deficiency in most cases.[31
] However, there were none with TBI or SAH in our cohort. This could be due to lack of awareness in clinicians attending these patients. Efforts need to be made to sensitize the clinicians about the existence of hypopituitarism in this subset of patients as advocated by a consensus guideline.[32
Central nervous infections, known to have high incidence in developing countries, are known to cause hypopituitarism. In a recent study from India, hypopituitarism was observed in about 30% of newly diagnosed TBM.[7
] The study stated TBM to be a severe stressful condition and conveniently used the controversial cortisol cut-off values for diagnosing adrenal insufficiency. The thyroid dysfunction could well be interpreted as sick euthyroid syndrome. Nevertheless, the study highlights the need to consider hypopituitarism in central nervous system (CNS) infections. Again, we did not have CNS infections as a cause of hypopituitarism in our series.
The etiology of hypopituitarism differs in childhood and non-tumor causes are more common than in adults. We previously reported treatment response to growth hormone therapy in 71 patients;[10
] hence, those cases (41 cases) which belonged to this center's endocrine OPD were excluded from the study. Among these children, 61 had abnormalities in hypothalamo-pituitary axis as a cause of GHD. Idiopathic GHD was reported in 73% which included 9.8% of combined pituitary hormone deficiency and 12.6% had GHD secondary to tumor/ structural lesion. Excluding subjects with genetic causes of hypopituitarism, craniopharyngioma is the most common cause of hypopituitarism in children rather than pituitary adenoma. One needs to consider congenital structural disease like Dandy Walker syndrome as a cause of pituitary dysfunction which has not been reported previously.
Contrary to the belief that hypophysitis occurs in middle-aged women, we previously reported a case of isolated lymphocytic hypothalamitis with panhypopituitarism in a 16-year-old girl.[14
] Familial hypopituitarism due to transcription factor defects is now a well-recognized entity[33
] and we documented two siblings with a novel PROP-1 mutation. The interesting fact was the deficiency of all the anterior pituitary hormones and early onset of corticotrophin deficiency in them.
We found that the most common presentation was due to compression symptoms rather than endocrine dysfunction. The fact highlights the subtleness in the clinical profile of patients with pituitary dysfunction and also underlines the need for dedicated evaluation of pituitary functions in those at risk of developing the same.
We noted acute presentation in the form of apoplexy in 15% of patients. Compared to one of the largest case series of classic pituitary apoplexy,[35
] we documented a very high rate of pituitary dysfunction—hypothyroidism (82.3% vs 45%), hypoadrenalism (70.5% vs 58%), hypogonadism (88.2% vs 43%), and diabetes insipidus (23.5% vs 6%). All had panhypopituitarism. This could be explained by delay in diagnosis of the subjects with pituitary adenomas.