Hypopituitarism, an underactive pituitary gland results from impaired production of one or more of the pituitary trophic hormones. Reduced pituitary function can result from inherited disorders, more commonly it is acquired and reflects mass effects of tumours or the consequence of trauma, infiltrative disorders, vascular and infectious aetiologies [1
Our patient had a congenital inherited disorder, aetiology of which was unknown as evidenced by Low TSH and ACTH in the period of stress, a low GH with a secondary hypothyroid background, secondary adrenocortical insufficiency. MRI also suggested a hypoplastic pituitary. Pituitary gland development from rathkes pouch involves a complex interplay of lineage specific transcription factors expressed in pleuripotent stem cells
and gradients of locally produced growth factors [1
The clinical manifestations of hypopituitarism depend on which hormones are lost and the extent of hormone deficiency.GH deficiency causes growth disorders in children and leads to abnormal body composition in adults. Gonadotrophin deficiency causes menstrual disorders and infertility in women and decreased sexual function, infertility and loss of secondary sexual characters in men. Somatotrophin and gonadotrophin seem to be affected first. TSH and ACTH deficiency usually develop later in the course of pituitary failure [3
TSH deficiency causes growth retardation in children and features of hypothyroidism in children and in adults. The secondary form of adrenal insufficiency caused by ACTH deficiency leads to decreased production of cortisol with relative preservation of mineralocorticoid
production. Prolactin deficiency causes failure of lactation. When lesions involve posterior pituitary, features like polyuria and polydipsia reflect loss of vasopressin secretion. Epidemiological studies have documented an increased mortality rate in patients with long standing pituitary damage primarily due to increased cardiovascular and cerebrovascular disease.
Our patient had a low free T3 and free T4 with a low TSH indicating a secondary hypothyroid state. This was the laboratory finding along with clinical suspicion which prompted us to investigate further.
The diagnosis of ACTH deficiency is difficult [2
]. Partial ACTH deficiency may be unmasked in the presence of an acute medical or surgical illness when clinically significant hypocortisolism reflects diminished ACTH reserve [1
]. Under surgical and anaesthetic stress, the adrenal glands secrete 116-185 mg of cortisol daily [4
]. Under maximum stress, they may secrete 200 to 500 mg/day [4
]. Good correlation exists between the severity and duration of the operation and the response of the adrenal gland. Major surgery would be represented by procedures such as major vascular, skeletal, neurologic repairor major reconstruction of the gastrointestinal tract and minor surgery by procedures such as herniorrhaphy. In one study of 20 patients during major surgery, the mean maximal concentration of cortisol
in plasma was 47 µg/dl (Range 22 to 75 µg/dl). During minor surgery, the mean maximal concentration of cortisol in plasma was 28 µg/dl (Range 10 to 44 µg/dl) [3
In our case the hormonal assay of ACTH and cortisol postoperatively reflected a secondary adrenocortical insufficiency. Also preoperative ACTH level was in low normal range in a stressful situation, which depicted a pituitary pathology. The diagnoses of GH deficiency can be made by GH assays before and after stimulation tests such as clonidine test, Argenine test and insulin provoked hypoglycaemia
]. Our patient had a pre-existing hypoglycemia.
Glucocorticoid replacement therapy improves most features of ACTH deficiency [1
Because these patients cannot respond to stressful situations, it was traditionally recommended that they may be given a stress dose of glucocorticoids preoperatively [5
However, Symreng and colleagues gave 25 mg of hydrocortisone intravenously to adults at the start of the operative procedure followed by 100 mg intravenously over the next 24 hours and this regimen did not worsen the situation. As minimum dosage was required in our patient to avoid the side effects of steroid, this regimen became more attractive [6
The total daily dose of hydrocortisone replacement should not exceed 300 mg divided into 2-3 doses. Prednisolone 5 mg (morning dose) and 2.5 mg (evening dose) having fewer mineralocorticoid action and long duration of action is preferred in patients who are orally allowed to intake. Doses are increased several folds during periods of acute illness or stress [1
]. Hence our patient was administered a steroid
dosage regimen i.e. 50 mg hydrocortisone which might have been inadequate considering dosage and duration but is an issue of debate due to lack of strict guidelines.
In a well controlled study of glucocorticoid replacement in primates, the investigators clearly defined the life-threatening events that can be associated with inadequate perioperative corticosteroid replacement [7
]. L-thyrorine is recommended in 0.075-0.15 mg daily dose till patient is euthyroid [1
]. Replacement of GH is indicated only if the diagnosis of adult GH deficiency is unequivocally established. If evolved GH<0.3 ng/ml then, in adults somatotrophin 0.1-1.25 mg subcutaneously four times daily and in children 0.02-0.05 mg /kg/day administered for around 6 months [1
]. In our case as adult growth hormone deficiency (AGHD) was not established, GH replacement was not considered. Difficult airway management, hypotension not responding to standard regimen, decrease in core body temperature in spite of active warming, very low concentration of anaesthetic drug requirement due to reduced metabolism, higher incidence of postoperative gastrointestinal and neuropsychiatric complications, electrolyte and coagulation disturbances, delayed emergence from anaesthesia, perioperative stress management, steroid management are the main highlights of perioperative vigilant anesthetic care [8
]. In patients with concurrent thyrotrophin and corticotrophin
deficiency, thyroxin must not be given without cortisol as this may precipitate a pituitary crisis [2
The response to surgical and traumatic stress is triggered by hypothalamic activation secondary to afferent neuronal input from an area of injury or emotional activity centered in the limbic system and humoral factors such as inflammatory cytokines
(interleukins, tumour necrosis factor and interferon). This is characterized by an increase in plasma levels of cortisol, ACTH, antidiuretic hormone/ vasopressin (ADH), renin, catecholamines, endorphins and by metabolic changes such as hypoglycemia and negative nitrogen balance [12
]. Regional anaesthesia and general anaesthesia appears to blunt the release of various stress hormones [15
]. Hence in this case epidural analgesia was considered.
Since it was a predicted difficult airway with history of hoarseness and as indirect laryngoscopy by otorhinolaryngologists was inconclusive we planned to evaluate the airway preoperatively so that peroperative airway management can be planned accordingly [16
After excluding any major upper airway problem, we decided to go for awake fibreoptic intubation as per difficult airway algorithm, keeping in mind all the required precautions and keeping all the resuscitation drugs and equipments ready [19
]. Maximum secretion of ACTH occurs during reversal of anaesthesia, during extubation and in immediate postoperative period [21
]. In the postoperative stressed state ACTH and cortisol increases 2-3 folds with circadian rhythm
disruption more in women [3
This lady postoperatively revealed a low normal cortisol and ACTH which showed that secondary adrenocortical insufficiency might have been one of the probable causes of intraoperative hypotension though epidural analgesia induced hypotension can’t be negated or proved.