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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 4  |  Issue : 3  |  Page : 163-166

Profile of adult hypopituitarism: A single-center experience


1 Department of Endocrinology, Pushpagiri Institute of Medical Sciences, Thiruvalla, Kerala, India
2 Department of Medicine, Pushpagiri Institute of Medical Sciences, Thiruvalla, Kerala, India

Date of Web Publication9-Dec-2015

Correspondence Address:
Rajeev Philip
Department of Endocrinology, Pushpagiri Institute of Medical Sciences, Thiruvalla, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0521.171431

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  Abstract 

Context: The incidence of hypopituitarism in the general population is 4 in 100,000, but there is a paucity of data on hypopituitarism. There are only two studies published from India on hypopituitarism. Aims: To study the clinical profile of hypopituitarism in a tertiary care center in Kerala. Settings and Design: This study was carried out in patients attending medicine and endocrinology outpatient and inpatient departments in Pushpagiri Medical College Hospital, Tiruvalla, Kerala between September 2013 and November 2014. Subjects and Methods: The study included 36 subjects of adult acquired hypopituitarism. Relevant clinical, hormonal, and imaging data were collected. Dynamic testing was done when necessary. Deficiency of hormones was defined based on standard recommendations. Results: The mean age was 48.6 years. There were 22 (59%) males and 14 females (41%). The most common presentation included altered sensorium (44.4%), hypogonadism, and menstrual irregularity (22.22%). As for the etiology of hypopituitarism, tumors (pre- and post-operative) comprised 58.3% of cases. Empty sella was found in 19.4% of patients with postsnake bite hypopituitarism (Simmonds syndrome) in 13.8%. Panhypopituitarism was seen in 86% of patients. Conclusions: Hypopituitarism is much more common than previously thought, and there is a delay in diagnosis either due to clinical inertia or due to its late and subtle presentation. The most common cause of hypopituitarism in a tertiary care center is pituitary tumors, and the most common presenting complaint is altered sensorium.

Keywords: Hypopituitarism, pituitary mass, Sheehan's syndrome, Simmonds syndrome


How to cite this article:
Philip R, John SM, Asokan A, Sarojiniyamma C S, Tomy LG, Charamelsankaran K. Profile of adult hypopituitarism: A single-center experience. Saudi J Health Sci 2015;4:163-6

How to cite this URL:
Philip R, John SM, Asokan A, Sarojiniyamma C S, Tomy LG, Charamelsankaran K. Profile of adult hypopituitarism: A single-center experience. Saudi J Health Sci [serial online] 2015 [cited 2019 May 19];4:163-6. Available from: http://www.saudijhealthsci.org/text.asp?2015/4/3/163/171431


  Introduction Top


Hypopituitarism, which is defined as partial or complete insufficiency of pituitary hormones, is a disease of varied etiologies. Earlier thought to be a rare disease, hypopituitarism was estimated to have an incidence of 12–42 cases/million/year and a prevalence of 300–455/million.[1] However, recent studies have shown that this disease much more common than previously thought, and the incidence of hypopituitarism in the general population is 4 in 100,000 population.[2] In spite of the development of sensitive hormonal assays and better pituitary imaging methods, hypopituitarism remains an underdiagnosed disease. Lack of awareness and clinical inertia is thought to be a cause of this under diagnosis, but the varied presentations of hypopituitarism, its nonspecific symptoms, and indolent course also contributes to the diagnostic confusion. In spite of hypopituitarism being a silent killer, causing increased mortality with cardiovascular cause and causing major impairment to the quality of life,[3] there is a paucity of data on hypopituitarism. There are only two studies published from India on of hypopituitarism, and ours is the only study from Kerala looking into the causes, presentation, and clinical features of hypopituitarism.

Aims and objectives

To study the clinical profile of hypopituitarism in a tertiary care center in Kerala.


  Subjects and Methods Top


This study was carried out in patients attending medicine and endocrinology outpatient department (OPD) and inpatient department in Pushpagiri Medical College Hospital, Tiruvalla, Kerala between September 2013 and November 2014. All new patients were studied prospectively, and those diagnosed before September 2013 were studied retrospectively. Patients diagnosed after the age of 15 years were included in the study. Relevant clinical, hormonal, and imaging data were collected. Dynamic testing for pituitary functions was carried out as necessary. Hypopituitarism was defined as a deficiency of one or more pituitary hormone, and panhypopituitarism was defined as a deficiency of three or more pituitary hormones.

Hormone levels were assessed using the multiparametric immunoassay system by VIDAS (USA) or using Immunotech, Beckman Coulter, France. Secondary hypothyroidism was defined as low free thyroxine (FT4, normal 9.0–16 pmol/L) with low or inappropriately normal thyroid-stimulating hormone (TSH, normal 0.35–5.4 μIU/ml). An AM cortisol of <3 μg/dl or a peak ACTH-stimulated cortisol of <18 μg/dl constituted adrenal insufficiency. Growth hormone deficiency (GHD) was defined when peak stimulated growth hormone level was <5 ng/ml (insulin tolerance test and/or clonidine stimulation test). GHD was also defined as low age- and sex-matched insulin-like growth factor I in the presence of panhypopituitarism.[4] Secondary hypogonadism in male was defined as low total testosterone (<3 ng/ml) and low or inappropriately normal luteinizing hormone (LH, normal 3–10 IU/l) and follicular-stimulating hormone (FSH, normal 3–10 IU/l) with clinical symptoms. Similarly, secondary hypogonadism in female was defined as low estradiol (<45 pg/ml) and low or inappropriately normal LH and FSH with amenorrhea.


  Results Top


A total of 49 patients with hypopituitarism were screened for the study. Hypopituitarism constitutes 3.8% of the endocrine OPD patients. From the total of 49 patients screened, 13 patients were excluded as they were of <15 years, (7/13), or because they had developmental or congenital defects of pituitary, which were diagnosed later (5/13). The study included 36 subjects of adult acquired hypopituitarism. The mean age was 48.6 years. There were 22 (59%) males and 14 females (41%). The most common presentation included altered sensorium (44.4%), hypogonadism, and menstrual irregularity (22.22%). 13.8% patients presented with pituitary apoplexy. 8.3% patients were diagnosed following evaluation of pituitary masses [Table 1].
Table 1: Presenting complaints of hypopituitarism

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As for the etiology of hypopituitarism, tumors (pre- and post-operative) comprised 58.3% of cases. Empty sella was found in 19.4% of patients, with postsnake bite hypopituitarism (Simmonds syndrome) in 13.8%, Sheehan's syndrome in 5.5%, and lymphocytic hypophysitis in 3% causing hypopituitarism in the rest [Table 2]. Hypogonadism (94.4%) was the most common abnormality seen followed by GHD (80.5%) and hypothyroidism (80.5%). Hypoadrenalism was seen in 66.6% of patients. Panhypopituitarism was seen in 86% of patients. The posterior pituitary deficiency was seen in 4 (11.1%) patients and all postpituitary surgery [Table 3].
Table 2: Etiology of hypopituitarism

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Table 3: Hormone deficiencies in hypopituitarism

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  Discussion Top


Hypopituitarism, a disease of varied etiologies, is a serious endocrine illness that requires early recognition and prompt treatment to avoid its severe deleterious effects. Hypopituitarism contributes to the mortality and morbidity by adrenal crisis and by increasing the cardiovascular mortality.[5],[6],[7] In adults, it is often missed due to nonspecific symptoms of GHD and hypogonadism or mild deficiencies of other pituitary hormones.[8]

There are only two studies from India until the date on the etiology of panhypopituitarism.[9],[10] Both the studies, Chatterjee et al., and Gundgurthi et al., report that the most common cause of adult panhypopituitarism is a pituitary tumor. Our study also noted the same, put the presentation of pituitary masses were different, with our study population having a higher incidence of pituitary apoplexy at presentation. This probably is due to the delayed diagnosis of pituitary tumors or hypopituitarism.

Another common presentation was postoperative pituitary masses for which radiotherapy was given to shrink the tumor or prevent recurrence. Some of these patients developed delayed panhypopituitarism as seen in 2 patients in our series. This brings out the importance of evaluating the pituitary status on follow-up, for patients receiving radiotherapy for sellar as well as other intracranial tumors.[11]

As expected, Kerala, with its higher standards of maternal health care had a low incidence of Sheehan's syndrome.

Postsnake bite panhypopituitarism in our study is much more common than described in the other two studies. Postviper bite panhypopituitarism is a well-described entity, but there are no well-documented studies from India on the exact incidence of postsnake bite hypopituitarism.[12],[13],[14] With an average 200,000 people bitten by snakes every year, and vipers contributing to the majority of these bites, the incidence definitely would be higher. One interesting observation which we found was that all the three patients were diagnosed late, with a mean delay of 12 years postviper bite. Furthermore, surprisingly, we found that all these patients had delay in onset of symptoms with a mean delay of 3.5 years. This lead us to hypothesize that the pituitary damage in postsnake bite hypopituitarism is not a single time event, but a gradual loss of pituitary function initiated by the snake bite, which results in a delayed appearance of symptoms. The possible explanation is drawn from the analogy of Sheehan's syndrome presenting late, where the late presentation is due to an autoimmune destruction, initiated by the vascular insult to the pituitary (postpartum bleed/snake bite).[15]

As opposed to western literature, most of the patients had panhypopituitarism, which probably is due to the delay in diagnosis of the pituitary tumors.

Another interesting fact was the mode of presentation of these patients. The majority of our patients had altered sensorium has their chief presenting complaint, and all these patients were found to have hyponatremia. Most of them had recurrent episodes of hyponatremia, requiring multiple hospitalizations. This presentation, which is different from what is described in literature, is probably due to the late diagnosis of the illness, and suggests the importance of assessing thyroid (FT4 and TSH) and cortisol status in any patient presenting with hyponatremia.[16]

As for the utility of magnetic resonance imaging in the diagnosis of hypopituitarism, it yields a positive diagnosis in 91% of the cases [Figure 1],[Figure 2],[Figure 3],[Figure 4].
Figure 1: Postsnake bite - panhypopituitarism

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Figure 2: Pituitary mass - panhypopituitarism

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Figure 3: Primary hypophysitis - panhypopituitarism

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Figure 4: Craniopharyngioma - panhypopituitarism

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  Conclusions Top


Hypopituitarism is much more common than previously thought, and there is a delay in diagnosis either due to clinical inertia or due to its late and subtle presentation. The most common cause of hypopituitarism in a tertiary care center is pituitary tumors, and the most common presenting complaint is altered sensorium. Panhypopituitarism is present in majority (85%) cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ascoli P, Cavagnini F. Hypopituitarism. Pituitary 2006;9:335-42.  Back to cited text no. 1
    
2.
Lamberts SW, de Herder WW, van der Lely AJ. Pituitary insufficiency. Lancet 1998;352:127-34.  Back to cited text no. 2
    
3.
Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet 2007;369:1461-70.  Back to cited text no. 3
    
4.
Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update. Endocr Pract 2009;15 Suppl 2:1-29.  Back to cited text no. 4
[PUBMED]    
5.
Rosén T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990;336:285-8.  Back to cited text no. 5
    
6.
Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 2001;357:425-31.  Back to cited text no. 6
    
7.
Bates AS, Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996;81:1169-72.  Back to cited text no. 7
    
8.
Brar KS, Garg MK, Suryanarayana KM. Adult hypopituitarism: Are we missing or is it clinical lethargy? Indian J Endocrinol Metab 2011;15:170-4.  Back to cited text no. 8
    
9.
Gundgurthi A, Garg MK, Bhardwaj R, Brar KS, Kharb S, Pandit A. Clinical spectrum of hypopituitarism in India: A single center experience. Indian J Endocrinol Metab 2012;16:803-8.  Back to cited text no. 9
    
10.
Chatterjee P, Mukhopadhyay P, Pandit K, Roychowdhury B, Sarkar D, Mukherjee S, et al. Profile of hypopituitarism in a tertiary care hospital of eastern India – Is quality of life different in patients with growth hormone deficiency? J Indian Med Assoc 2008;106:384-5, 388.  Back to cited text no. 10
    
11.
Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, Neelis KJ, Biermasz NR, Romijn JA, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: Systematic review and meta-analysis. J Clin Endocrinol Metab 2011;96:2330-40.  Back to cited text no. 11
    
12.
Uberoi HS, Achuthan AC, Kasthuri AS, Kolhe VS, Rao KR, Dugal JS. Hypopituitarism following snake bite. J Assoc Physicians India 1991;39:579-80.  Back to cited text no. 12
    
13.
Majunder AK. Hypopituitarism following snake bite. J Assoc Physicians India 1992;40:414.  Back to cited text no. 13
    
14.
James E, Kelkar PN. Hypopituitarism after viperine bite. J Assoc Physicians India 2001;49:937-8.  Back to cited text no. 14
    
15.
Goswami R, Kochupillai N, Crock PA, Jaleel A, Gupta N. Pituitary autoimmunity in patients with Sheehan's syndrome. J Clin Endocrinol Metab 2002;87:4137-41.  Back to cited text no. 15
    
16.
Melmed S, Jameson JL. Disorders of anterior pituitary and hypothalamus. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 18th ed. New York: The McGraw-Hill Companies Inc.; 2012. p. 2876-902.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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