A Comprehensive Review of Empty Sella and Empty Sella Syndrome.

OBJECTIVE: Incidental radiographic findings of an empty sella are prevalent in up to 35% of the general population. While empty sella was initially considered clinically insignificant, a subset of patients exhibits endocrine or neuro-ophthalmologic manifestations which are diagnostic of empty sella syndrome (ESS). Recent studies suggest that more patients are affected by ESS than previously recognized, necessitating a deeper understanding of this condition. This comprehensive review describes a practical approach to evaluating and managing ESS. METHODS: Literature review was conducted on etiologies and risk factors associated with primary and secondary empty sella, the radiologic features that differentiate empty sella from other sellar lesions, and the role of clinical history and hormone testing in identifying patients with ESS, as well as treatment modalities. RESULTS: Pituitary function testing for somatotroph, lactotroph, gonadotroph, corticotroph, and thyrotroph abnormalities is necessary when suspecting ESS. While an isolated empty sella finding does not require treatment, ESS may require pharmacologic or surgical interventions to address hormone deficits or intracranial hypertension. Targeted hormone replacement as directed by the endocrinologist should align with guidelines and patient-specific needs. Treatment may involve a multidisciplinary collaboration with neurology, neurosurgery, or ophthalmology to address patient symptoms. CONCLUSION: This review underscores the evolving understanding of ESS, stressing the significance of accurate diagnosis and tailored management to mitigate potential neurologic and endocrine complications in affected individuals.

A case of Empty Sella syndrome with adrenal insufficiency masked by prednisolone after administration of immune checkpoint inhibitors.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is gradually increasing; ICIs produce a variety of immune-related adverse events (irAEs), especially ICI-induced hypoadrenocorticism, which can be a lethal complication if treatment is delayed. PATIENT CONCERNS: A 63-year-old man received chemotherapy with pembrolizumab for nonsmall cell lung cancer. He developed drug-induced interstitial pneumonia 366 days after receiving pembrolizumab and was treated with prednisolone. Five hundred thirty-seven days later, he developed drug-induced eosinophilic enteritis, and pembrolizumab was discontinued and prednisolone was continued. After discontinuation of prednisolone, general malaise and edema of the lower extremities appeared, and adrenal insufficiency was suspected. DIAGNOSIS: In blood tests on admission adrenocorticotropic hormone (ACTH) was 2.2 pg/mL and cortisol was 15 µg/dL, with no apparent cortisol deficiency. However, the cortisol circadian rhythm disappeared and remained low throughout the day; a corticotropin-releasing hormone stimulation test showed decreased reactive secretion of ACTH. Pituitary magnetic resonance imaging showed pituitary emptying, suggesting Empty Sella syndrome. INTERVENTIONS AND OUTCOMES: We started hydrocortisone and his symptoms were improved. CONCLUSIONS: The administration of high-dose steroids after ICI administration may mask the symptoms of hypoadrenocorticism as irAEs. Therefore, we should bear in mind the possibility of hypoadrenocorticism when we stop steroid therapy in patients who are treated with steroids after ICI administration.

Pituitary Dysfunction in Idiopathic Intracranial Hypertension: An Analysis of 80 Patients.

BACKGROUND: Empty sella is a commonly described imaging entity in patients with idiopathic intracranial hypertension (IIH). Though menstrual and hormonal disturbances have been associated with IIH, available literature lacks systematic analysis of pituitary hormonal disturbances in IIH. More so, the contribution of empty sella in causing pituitary hormonal abnormalities in patients of IIH has not been described. We carried out this study to systematically assess the pituitary hormonal abnormalities in patients with IIH and its relation to empty sella. METHODS: Eighty treatment naïve patients of IIH were recruited as per a predefined criterion. Magnetic resonance imaging (MRI) brain with detailed sella imaging and pituitary hormonal profile were done in all patients. RESULTS: Partial empty sella was seen in 55 patients (68.8%). Hormonal abnormalities were detected in 30 patients (37.5%), reduced cortisol levels in 20%, raised prolactin levels in 13.8%, low thyroid-stimulating hormone (TSH) levels in 3.8%, hypogonadism in 1.25%, and elevated levels of gonadotropins were found in 6.25% of participants. Hormonal disturbances were independent and were not associated with the presence of empty sella (p = 0.493). CONCLUSION: Hormonal abnormalities were observed in 37.5% patients with IIH. These abnormalities did not correlate with the presence or absence of empty sella. Pituitary dysfunction appears to be subclinical in IIH and responds to intracranial pressure reduction, not requiring specific hormonal therapies.

Anterior hypopituitarism due to primary empty sella syndrome in a critically unwell patient.

A previously fit and well male in his early 40s, presented to the emergency department, hypotensive, bradycardic and hypothermic with reduced levels of consciousness after being found diaphoretic and unwell at his home. Despite fluid resuscitation with warmed saline, he remained hypotensive and required vasopressor support leading to intensive care admission. Initially, the patient was managed for suspected meningoencephalitis but was later found to have hypopituitarism leading to secondary hypothyroidism and adrenal insufficiency. Subsequent investigations revealed it is due to empty sella syndrome.

The 1 µg Synacthen stimulation test in the diagnosis of secondary adrenal insufficiency in patients with Rathke's cleft cyst and empty sella syndrome.

INTRODUCTION: Rathke's cleft cyst (RCC) and primary empty sella syndrome (PESS) are usually incidental findings on magnetic resonance imaging (MRI) scans. In most cases, these lesions do not cause mass effect symptoms and do not require surgical intervention. In patients with RCC or PESS, it is important to exclude secondary adrenal insufficiency (SAI), which may be a life-threatening condition. MATERIAL AND METHODS: The incidence of SAI was assessed in patients with RCC or PESS detected by MRI, using the 1 µg Synacthen stimulation test. A total of 38 patients were analysed. Test results were linked to clinical symptoms and the type of cystic lesion. RESULTS: Assuming that cortisol levels < 14.6 µg/dL in Synacthen test are the criterion of SAI diagnosis, SAI was diagnosed only in 2 patients (5%). Adopting the traditional criterion of cortisol levels < 18 µg/dL, SAI would be diagnosed in 7 patients (18.4 %). Dizziness (Chi2 = 3.89; p = 0.049) and apathy (Chi2 = 3.87; p = 0.049) were significantly more frequent in the PESS group than in the RCC group. CONCLUSIONS: The incidence of SAI in the general patient population with empty sella syndrome and Rathke's cleft cysts is low. The 1 µg Synacthen test seems to be a valuable tool in the diagnosis of SAI among patients with RCC and PESS. Further studies are necessary to determine the sensitivity and specificity of the 1 µg Synacthen test with the standardization of test protocol and considering the cortisol level at the 20-minute timepoint. PESS patients report dizziness and apathy more frequently than RCC patients, which does not result from the disturbance of the hypothalamic-pituitary-adrenal axis, but probably from the different pathogenesis of these cystic lesions.

Hyponatremia due to adrenal insufficiency after a Mamushi bite: a case report.

BACKGROUND: Mamushi bites are the most common venomous snake bites in Japan, with known complications including rhabdomyolysis and acute kidney injury; however, adrenal insufficiency as a result of snake bites has not been previously reported. We report a case of empty sella with transient adrenal insufficiency during hospitalization for a Mamushi bite. CASE PRESENTATION: An 84-year-old man was admitted to our hospital with a Mamushi bite on the right fifth finger. Serum sodium (Na) level remained in the normal range. On the ninth day of admission, he developed hyponatremia, with a serum Na level of 114 mEq/L and serum cortisol level of 4.0 µg/dL (reference value 4.5-21.1 µg/dL). His serum Na level was restored within the normal range after administration of corticosteroids with 3% NaCl solution. Both rapid adrenocorticotrophin and corticotropin-releasing hormone loading tests showed low cortisol response. Based on the results of the hormone loading tests, a diagnosis of pituitary adrenal insufficiency was made. Contrast-enhanced pituitary magnetic resonance imaging (MRI) showed primary empty sella. After discontinuation of corticosteroids, the hyponatremia did not recur, and the patient was discharged on the 24th day of hospitalization. After discharge, the patient visited an outpatient clinic, but hyponatremia recurrence was not observed. CONCLUSIONS: This is the first report of hyponatremia due to pituitary adrenal insufficiency during hospitalization for a Mamushi bite in a patient with empty sella. When hyponatremia occurs during hospitalization for a Mamushi bite, cortisol measurement, hormone loading test, and head MRI should be performed to search for pituitary lesions because of the possibility of adrenal insufficiency caused by snake venom.

Intractable hyponatremia secondary to syndrome of inappropriate antidiuresis complicated with empty sella: A case report.

RATIONALE: Hyponatremia is a common electrolyte disorder in elderly critically ill patients, and it may be associated with poor outcomes, higher morbidity, and mortality. Syndrome of inappropriate antidiuresis (SIAD) is one of the main causes of hyponatremia, with an insidious onset that is highly misdiagnosed. Primary empty sella lesions are specific, mostly asymptomatic, and easily overlooked. SIAD combined with empty sella is much rarer in clinic, this article focuses on the diagnosis and management of an elderly patient with intractable hyponatremia secondary to syndrome of inappropriate antidiuresis complicated with empty sella. PATIENT CONCERNS: An 85-year-old male patient with severe pneumonia presented with progressive and intractable hyponatremia. DIAGNOSES: The patient had clinical signs of persistent hyponatremia, low plasma osmolality, elevated urinary sodium excretion, and hyponatremia that worsened with increased intravenous rehydration and was effective with appropriate fluid restriction. The diagnosis of SIAD combined with empty sella was made in combination with the findings of the pituitary and its target gland function. INTERVENTIONS: Numerous screenings were performed to clarify the cause of hyponatremia. His overall condition was poor due to recurrent episodes of hospital-acquired pneumonia. We treated with ventilation support, circulatory support, nutritional support, anti-infection, and continuous correction of electrolyte imbalance. OUTCOMES: His hyponatremia gradually improved through aggressive infection control, appropriate fluid restriction (intake controlled at 1500-2000mL/d), continuous electrolyte correction, supplementation with hypertonic salt solution, and potassium replacement therapy. LESSONS: Electrolyte disorders, especially hyponatremia, are very common in critically ill patients, but the etiology of hyponatremia is challenging to diagnose and treat, and timely attention and proper diagnosis of SIAD and individualized treatment are the significance of this article.

Hand-Schüller-Christian syndrome combined with empty sella syndrome: A case report and literature review.

RATIONAL: Hand-Schüller-Christian syndrome (HCS) is a rare disease with little clinical awareness, but the condition is more dangerous, and it combines with empty sella syndrome (ESS) which is extremely rare. PRESENTATION: A 26-year-old male patient who had proptosis, headaches, and diabetes insipidus for more than 10 years, and chronic cough and wheeze for 8 years presented to our hospital due to an abrupt onset of chest pain for 2 days. DIAGNOSIS: Hand-Schüller-Christian syndrome is diagnosed based on the typical clinical manifestations of diabetes insipidus and bilateral proptosis, magnetic resonance imaging (MRI) pituitary imaging and pathology. Empty sella syndrome is diagnosed based on hormonal indicators, clinical manifestations and MRI pituitary scan results. Type 1 respiratory failure and severe pneumonia can be diagnosed based on the results of clinical examination, chest imaging (including chest x-ray and computed tomography), pathology and blood gas analysis. Left pneumothorax can be diagnosed with chest imaging. INTERVENTIONS: "Meropenem and Cefdinir" were given for antimicrobrial coverage, "Desmopressin acetate" for anti-diuretic treatment, "Forcodine" for cough relief, "Ambroxol and acetylcysteine" for phlegm reduction, and continuous closed chest drainage was performed. OUTCOMES: The patient discharged after cough, wheezing, headache and other symptoms improved, and vital signs were stable. The patient has been followed up once a month for 17 months ongoing after discharge. At present, symptoms such as cough, sputum, and wheezing have improved considerably, and the mMRC score of dyspnea is 2 points. The reexamination of the chest X-ray shows that the absorption of lung exudates is better than before, and there is no recurrence of pneumothorax. LESSONS: Consider whether isolated diabetic insipidus is related to HSC, and if so, conduct an MRI, a biopsy, and other examinations as soon as possible.

Primary empty sella syndrome-caused rhabdomyolysis misdiagnosed as recurrent sepsis: a case report and literature review.

We reported a case of a 68-year-old man who presented with recurrent fever and multiorgan dysfunction. His significantly elevated procalcitonin and C-reactive protein levels indicated recurrent sepsis. However, no focus of infection and no pathogens were identified through a variety of examinations and tests. Although the increase of creatine kinase was less than five times the upper limit of normal value, the diagnosis of rhabdomyolysis secondary to adrenal insufficiency resulting from primary empty sella syndrome was finally made, as supported by serum myoglobin elevation, serum cortisol, and adrenocorticotropic hormone deficiency, bilateral adrenal atrophy on computed tomography, and empty sella on magnetic resonance imaging. After the glucocorticoid replacement treatment, the patient's myoglobin gradually returned to normal range, and his condition continued to improve. Rhabdomyolysis resulting from a rare cause may be misdiagnosed as sepsis in patients who present with increased procalcitonin levels.

Myopathic syndrome revealing a rare condition: Sheehan syndrome, a case-based review.

This report presents a case of a Sheehan syndrome diagnosed with a delay of 29 years after occurrence of first symptoms, following a laborious birth ended with dead fetus and massive hemorrhage. The 50-year-old patient, with early menopause from the age of 21, is referred to our rheumatology department to investigate the etiology of a myopathic syndrome, which started 2 months before and gradually worsened. The differential diagnosis took into consideration the autoimmune, infectious, paraneoplastic, endocrinological, and drug-induced myopathic syndrome. Paraclinical investigations revealed panhypopituitarism, and cerebral magnetic resonance imaging detected empty-sella. The etiology of a myopathic syndrome is often multifactorial; therefore, it is important to continue the investigations even after identifying one possible etiological factor, especially when it does not seem to fully explain the clinical-paraclinical picture. Usually, the multiple dimensions of panhypopituitarism bring the patient to various medical specialties depending on the dominant symptomatology. Given the rarity of the above-mentioned syndrome in the present, and the long gap between the initial event and the final diagnosis, its identification continues to be a challenge.

Analysis of clinical features of primary empty sella.

OBJECTIVE: A retrospective analysis of clinical data of 60 patients with primary empty sella (PES) was conducted to further improve the understanding of the disease. METHODS: The clinical data of 60 patients diagnosed with PES admitted to the Department of Endocrinology of Wuhan Union Hospital for different reasons from January 2000 to September 2018 were analyzed. RESULTS: The 60 cases comprised 22 (36.67%) male and 38 (63.33%) female patients, for a male-to-female ratio of 1:1.73. There was predominance of 50-59 year-olds and women with multiple pregnancies. Of the 60 patients, 41.67% showed fatigue, 26.67% dizziness and headache, 21.67% nausea and vomiting, 18.33% anorexia, and 6.67% visual impairment and other symptoms. Twenty-seven patients (45.0%) had normal pituitary function, and 33 (55.0%) had hypopituitarism. Complete PES was more prone to result in hypopituitarism than partial PES. Men with PES were more likely to have hypopituitarism than women. CONCLUSION: The incidence of PES was significantly higher in women than in men; PES was common in middle-aged and older women with multiple pregnancies. Symptoms were diverse and clinical manifestations may lack specificity compared to other diseases and need to be differentiated. About half of PES patients may develop hypopituitarism. Therefore, for patients with empty sella detected on magnetic resonance imaging (MRI) with or without clinical symptoms, the pituitary function should be thoroughly and promptly evaluated.

Successful Electroconvulsive Therapy in Idiopathic Intracranial Hypertension With Mood Disorder and Partial Empty Sella Syndrome.

ABSTRACT: Patients with idiopathic intracranial hypertension (IIH) often experience significant burden from psychiatric comorbidities. Mood disorders are present in up to half of all patients with IIH, and they are often refractory to treatment by psychopharmacologic agents. Electroconvulsive therapy (ECT) is the criterion standard for treatment of patients with the most severe psychiatric burden but has relative contraindications in those possessing pathologies that raise intracranial pressure (ICP). There is a growing body of literature that a multidisciplinary care model would allow for patients with elevated ICP to receive ECT safely. Despite the high prevalence of mood disorders in patients with IIH, there are only 2 published case reports describing ECT delivery to patients from this cohort. We report our own case of a patient with IIH and major depressive disorder who received 38 bitemporal treatments with a positive response and no change in baseline ICP. Her positive response, along with the absence of elevation of ICP, aligns with the prior reports; however, her IIH symptoms have not responded as reported in the 2 cases-despite receiving more than 4 times the amount of treatments. Moreover, our patient possessed unique imaging for a partial empty sella syndrome, which has recently been found to be the only significant finding in patients who had a mood disorder before IIH diagnosis, versus a mood disorder developing after IIH diagnosis. This case serves to provide evidence of the safety and success of ECT in patients with IIH, relying on multidisciplinary care from psychiatry, neurology, and neuro-ophthalmology.

The coexistence of newly diagnosed acromegaly with primary empty sella: More frequent than expected?

OBJECTIVE: We investigated the coexistence of newly diagnosed acromegaly with primary empty sella (ES), which is considered to be a rare association, and the impact of ES on the laboratory, radiological and prognostic status of acromegaly. DESIGN: Acromegaly patients diagnosed and followed-up between 2012 and 2021 were included. Empty sella was defined as the pituitary gland and adenoma filling <50% of the sella turcica on preoperative T1 magnetic resonance imaging (MRI). RESULTS: 102 acromegalic patients (45 male, 57 female, 45.5 ± 12.8 (range: 20-70 years) were included and data of a median 3 years (range: 0.5-9 years) were presented. ES was detected in 19 (18.6%) patients and 4 had complete and 15 had partial ES. Although not significant, adenoma size and residual adenoma on MRI on postoperative 3rd month, and disease remission at last control were lower in acromegaly with ES than in acromegaly without ES, while the rate of female gender and remission on postoperative 3rd month were higher. While preoperative serum prolactin and nadir GH responses to OGTT were significantly lower in patients with ES, there was no difference in terms of other pituitary hormones among both groups. CONCLUSION: The present study revealed the coexistence of newly diagnosed acromegaly with primary ES at a rate of nearly 20% which is more frequent than expected and this association is not rare. The presence of ES was not associated with any preoperative/postoperative pituitary hormone levels and remission status, except lower preoperative prolactin and nadir GH responses to OGTT.

Clinical course of primary empty sella in children: a singlecenter experience.

BACKGROUND: Various studies, mainly conducted in adults, have examined the hormonal axis in primary empty sella (PES), and reported various forms of pituitary deficiencies. We report our experience with PES in pediatric patients in terms of pituitary function, associated impairments, and responses to treatment. METHODS: We reviewed 10,560 cranial and 325 pituitary magnetic resonance imagings (MRIs) performed at our university hospital between January 2010 and December 2020 and identified patients with PES. Patients with additional abnormal MRI findings, a history of cranial surgery or radiotherapy, autoimmunity, long-term use of chemotherapeutic or immunosuppressive agents or incomplete diagnostic evaluation were excluded. Clinical, radiological and laboratory evaluations were recorded. RESULTS: The study included 17 patients [9 girls, 8 boys; median age 12.4 years (7.25, 4.3 - 17)]. The median size of the pituitary was 2 mm (0.7, 1.2 - 3). Based on age-dependent pituitary height measurements, fifteen (88%) patients had pituitary gland hypoplasia. Five patients presented with short stature, two had both pubertal delay and short stature, and one had pubertal delay. Nine patients presented with neurological symptoms such as headaches, tinnitus, tics, and dizziness. Five short patients had growth hormone deficiency. None of the patients had hyper- or hypoprolactinemia, adrenal insufficiency, hypothyroidism, or diabetes insipidus. There was statistically no significant association between the size of the pituitary gland and the severity of hypopituitarism (p = 0.42). CONCLUSIONS: The high incidence of pituitary dysfunctions ascertain that this entity should not be considered a normal variant but, should instead be carefully evaluated with appropriate basal and dynamic hormonal testing.

Demonstration of the inferior intercavernous sinus is closely linked to the extent of pneumatization of the sphenoid sinus: useful information for the pituitary surgeon.

PURPOSE: To study the utility of T2-weighted MRI sequences in the identification of the inferior intercavernous sinus (IICS), a potential source of bleeding during transsphenoidal surgery of pituitary adenomas. METHODS: Pituitary sagittal T1W and coronal T2W MRI sequences were analyzed in 237 consecutive patients, after the exclusion of postoperative MRIs and those revealing an empty sella or a pituitary macroadenoma. Sphenoid sinus pneumatization was defined as incomplete (group 1) if it did not reach the nadir of the sella turcica, as complete (group 2) if it extended beyond the nadir of the sella or asymmetric (group 3), when only one side of the sinus was completely pneumatized. RESULTS: In Group 2 (70% of the patients), the IICS was rarely visualized on coronal T2W MRI (6/167 patients-3.6%), whereas in Group 1 it was identified in nearly all patients (55/57 patients - 96.5%, p < 0.001). In Group 3, the IICS was only visible above the non-pneumatized part of the sphenoid sinus. CONCLUSIONS: The IICS can be identified on coronal T2W images in patients with an incompletely pneumatized sphenoid sinus, but very rarely in patients with a totally pneumatized sinus. This information can help to increase awareness among pituitary surgeons of the need to potentially manage IICS bleeding during transsphenoidal surgery in patients with an incompletely pneumatized sphenoid sinus.

A Multicenter Cohort Study in Patients With Primary Empty Sella: Hormonal and Neuroradiological Features Over a Long Follow-Up.

Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up. Design: multicenter retrospective cohort study enrolling patients referred between 1984-2020 to five Pituitary Units, with neuroradiological confirmed PES and a complete hormonal assessment. Methods: we analyzed hormonal (including basal and dynamic evaluations), clinical and neuroradiological data collected at diagnosis and at the last visit (at least 6 months of follow-up). Results: we recruited 402 patients (females=63%, mean age=51.5 ± 16 years) with PES (partial, total, undefined in 66%, 13% and 21%, respectively). Hypopituitarism was present in 40.5% (hypogonadism=20.4%, hypoadrenalism=14.7%, growth hormone deficiency=14.7%, hypothyroidism=10.2%, diabetes insipidus=1.5%; multiple deficiencies=11.4%) and hypeprolactinemia in 6.5%. Interestingly, hormonal alterations were diagnosed in 29% of incidental PES. Hypopituitarism was associated with male sex (p=0.02), suspected endocrinopathy (p<0.001), traumatic brain injury (p=0.003) and not with age, BMI, number of pregnancies and neuroradiological grade. A longitudinal assessment was possible in 166/402 (median follow-up=58 months). In 5/166 (3%), new deficiencies occurred, whereas 14/166 (8.4%) showed a hormonal recovery. A progression from partial to total PES, which was found in 6/98 patients assessed with a second imaging, was the only parameter significantly related to the hormonal deterioration (p=0.006). Conclusions: this is the largest cohort of patients with PES reported. Hypopituitarism is frequent (40%) but hormonal deterioration seems uncommon (3%). Patients need to be carefully evaluated at diagnosis, even if PES is incidentally discovered.

Different Cases of Short Stature.

This case sieries gives three different cases with three different presentation and different approaches to a patient with short stature. Material: CASE 1: A 13 Year old female brought by her parents with complaints of decreased height appropriate for age. O/E height- 127cm(<-3SD), weight 42kg, MPH- 150cm, arm span to height ratio- 1:1, secondary sexual characters- tanners stage 2. X-ray hand with wrist- bone age 0f 12 years. TFT- within normal limits. MRI pituitary- normal study. Patient suspected to have isolated growth harmone deficiency. Growth harmone stimulation test done after sex steroid priming which showed results of growth harmone deficiency. Patient started on 1.5mg growth harmone s/c per day. CASE 2: A 18 year old boy brought by his parents with complaints of decreased height appropriate for age and absence of facial, axillary and pubic hair. O/E height- 145cm, weight 55kg, MPH- 165cm, arm span to height ratio 1.1:1, external genitalia- male, testes in scrotum, testicular volume- 2.5ml, secondary sexual characters- tanners stage 1. Xray hand with wrist- bone age of 17years. TFT within normal limits. FSH, LH, testosterone levels were low. Growth harmone stimulation test after sex steroid priming showed low growth harmone levels. MRI pituitary showed empty sella. Patient diagnosed to have panhypopititarism and started on inj. Growth harmone 0.24mg/kg/week subcutaneous and inj.testosterone 100mg/month IM. CASE 3: A 17 year old female brought by her parents with complaints of decreased height appropriate for age and absent menstruation till date. O/E height- 143cm(<- 3SD), weight- 45 kg, MPH- 170cm, arm span to height ratio 1.1:1, external genitalia - female, secondary sexual characters - tanners stage 1. Xray hand with wrist - bone age of 16years. Further evaluation showed TSH-21.8. MRI pelvis showed streak gonads. Serum growth harmone and IGF levels within normal limits. Estradiol was low and FSH, LH were high. Karyotyping showed 45XO. Patient diagnosed to have turner's syndrome. Since x-ray showed non-closure of epiphysis, patient started on growth harmone 0.33 mg/kg/week and advised not to take estrogen till epiphyseal closure. Observation: case 1: functonal pituitary pathology Case 2: structural pituitary pathology Case 3: gonadal pathology Conclusion: Short stature can be a manifestation of isolated GH defeciency, Hypogonadotropic Hypogonadism or Hypergonadotropic hypergonadism.