Pituitary apoplexy (PA) which occurs due to ischemic or haemorrhagic infarction of pituitary adenomas is a serious and life-threatening complication (1). The reported incidence of PA changes between 0.6 and 10% of surgically resected adenomas in different series (1,2). PA often occurs spontaneously in pituitary macroadenomas and may be associated with varying degrees of pituitary insufficiency (2). In its classical form, PA presents with severe headache (93%), visual disturbances (75%), ocular palsy (68%), nausea and vomiting (37%), and mental status changes (22%) (2). However, sometimes intratumoral haemorrhage and necrosis occur without these signs, which is called subclinical PA (3). We present here the case of a patient who was referred to our endocrinology outpatient clinic with a preliminary diagnosis of acromegaly and was found to have hypopituitarism possibly due to a subclinical PA.
A 57-year-old male patient was observed to have acromegalic features in the gastroenterology outpatient clinic in which he was seen for epigastric pain and was referred to our endocrinology outpatient clinic. His main complaints were weakness and myalgia and he had not noticed any changes in his appearance. On physical examination, blood pressure was 130/90 mmHg, and the patient had typical acromegalic features involving frontal bossing, wide nasal bridges, thick lips, big ears and nose, an enlarged tongue, enlarged hands and feet and a deep resonant voice (Figure 1,2). The pupil size, ocular movements, visual fields, and optic fundi were normal. There were no meningeal signs or other neurological deficits. On personal history, he had been smoking two packs per day for forty-five years. He was not using any drugs or alcohol. The patient had not been hospitalized or in emergency unit for any reason, except the epigastric pain in the previous year.
On laboratory examination, complete blood count, renal and liver function tests were within normal limits. Fasting plasma glucose and insulin levels were in the normal ranges [82 (70-100) mg/dl, 3.19 (2.6-24.9) µIU/ml, respectively]. On endocrinological evaluation, his prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and free testosterone levels were within normal limits, but thyroid function tests were compatible with secondary hypothyroidism (Table 1). His basal growth hormone (GH) level was 0.24 (0.004-1.406) μg/l and insulin-like growth factor 1 (IGF-1) level was within normal limits for age and sex. As his basal GH level was under 0.4 μg/l, an OGTT-GH suppression test was not performed. On insulin tolerance test (ITT), there was no cortisol and GH response to hypoglycaemia (Table 2). Additionally, he had no symptoms or laboratory values compatible with posterior pituitary dysfunction.
On imaging, a haemorrhagic adenoma 9x6 mm in size in the right lateral wing of the sella was detected on T1-weighed pituitary MRI scan (Figure 3). Prednisolone and L-thyroxine replacement therapy were started. Three months later, a new pituitary MRI imaging revealed persistent pituitary adenoma of the same size. His serum free T4 level was within normal limits with L-thyroxine replacement therapy, but it was learnt that the patient had stopped taking prednisolone a few weeks ago.
A repeated ITT showed continuing secondary adrenal insufficiency and there was no GH response to hypoglycaemia either. An L-dopa stimulation test was also performed, in which there was no GH response either (data not shown). Nine months later, his IGF-1 levels were lower but still within normal limits and GH level was still <0.4 μg/l. As his tumor did not cause any compressive symptoms, a surgical intervention was not planned and he is under follow-up with hormone replacement therapy.
In this paper, we reported a male patient who had acromegaly, probably secondary to a pituitary somatotroph adenoma but now has hypopituitarism with secondary adrenal insufficiency and hypopituitarism. Interestingly, the patient did not have a history suggestive of PA like sudden onset of headache, nausea, vomiting and disturbance of consciousness or visual field defects, which on the other hand, further suggests the diagnosis of subclinical PA as the possible etiology of hypopituitarism. Although the patient’s physical findings were compatible with acromegaly, normal IGF-1 levels and basal GH level under 0.4 μg/l revealed inactive disease. Furthermore, he did not have GH response to ITT and L-dopa stimulation test. As lower than normal IGF-1 levels are not essentially required, absence of GH response to two stimulation tests confirms the diagnosis of GH deficiency in this patient (4).
The differential diagnosis of a patient with acromegalic features but normal plasma GH and IGF-1 levels includes pseudoacromegaly (5). Pseudoacromegaly is a rare syndrome, characterized by severe insulin resistance and acromegaloidism with accompanying normal GH and IGF-1 levels (5). Fasting insulin levels above 50-70 µU/ml or peak (post-OGTT) insulin levels above 350 µU/ml suggest severe insulin resistance, in contrast to the fasting serum insulin levels below 20 µU/ml or peak (post-OGTT) insulin levels below 150 µU/ml observed in normal individuals (5). Clinical findings associated with severe insulin resistance include acanthosis nigricans, consisting of velvety hyperpigmented and hyperkeratotic patches in skin fold areas, such as the nape of the neck, the axillae, and the groins (5). Additionally, impaired glucose tolerance or overt diabetes mellitus commonly but not always occurs at a later stage in these individuals. Regarding our patient, the diagnosis of pseudoacromegaly was ruled out with presence of normal fasting insulin levels. However, it should be noted that the existence of a pituitary adenoma, although strongly implies, does not confirm the diagnosis of a previous functioning somatotroph adenoma in this patient, as it was not biochemically confirmed.
The largest series (n=185) of subclinical PA in the literature is from Zhang and colleagues which included 14 (7.57%) patients with acromegaly (3). However, in this study, PA was not reported to occur during the treatment of hormonal excess states and all subjects in this group needed an operation for treatment of their pituitary adenomas.
On the other hand, in a recent review, Fraser and colleagues have presented a case and have also identified 21 additional cases in the literature who were "cured" of acromegaly after PA (6). In eight cases (36%), there was no previous formal diagnosis of acromegaly, as in our case. The only case with subclinical PA was a patient reported by Imaki and colleagues, who had a previous diagnosis of acromegaly and after a gastrointestinal bleeding his biochemical results were found to be normalized (7). For some of these cases, several different triggering events were identified such as head trauma, Gd-DTPA-administration for contrast-enhanced MRI, thyroidectomy, anticoagulation, cerebral angiography and pituitary CT imaging (6).
As a conclusion, in the differential diagnosis of patients with acromegalic appearance, although rare, pseudoacromegaly should be considered. Concomitant pituitary hormone and imaging abnormalities, as in our patient, can lead to a probable diagnosis of “acromegaly cured by subclinical PA”. However, further follow-up of these patients is essential for the existing adenoma, possible additional hormonal deficiencies or recurrence of acromegaly that can occur in later stages.
Address for Correspondence: Suleyman Ipekci, Selcuk University Meram School of Medicine, Endocrinology and Metabolism, Konya, Turkey
GSM: +90 533 720 20 27 E-mail: firstname.lastname@example.org Recevied: 01.07.2011 Accepted: 01.07.2011
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