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Magnetic resonance imaging of the brain in idiopathic hypogonadotropic hypogonadism
Clinical Radiology(1993) 48, 122 124
Magnetic Resonance Imaging of the Brain in Idiopathic Hypogonadotropic Hypogonadism S. BAJAJ, A. C. A M M I N I * , R. M A R W A H A t , P. G U L A T I t , K. KHETARPAL:~ and H. MAHAJANw
Department of Medicine, SRN Hospital, Allahabad, *Department of Endocrinology, Metabolism and Diabetes, Ansari Nagar, New Delhi, tDepartment of Radiology, NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, New Delhi, ~Department of Physiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, and w Institute of Imaging and Research, New Delhi, India Magnetic resonance imaging (MRI) of the pituitary, hypothalamus and olfactory sulci was performed in 40 patients with idiopathic hypogonadotropic hypogonadism (IHH). Twelve of these patients had an impaired sense of smell (Kallmann's syndrome). Sagittai and coronal imaging revealed no morphological abnormalities in the hypothalamic-pituitary region. On axial imaging rudimentary, hypoplastic or aplastic olfactory sulci were found in eight cases. All patients with olfactory sulcai abnormalities had associated hyposmia (one case) or anosmia (seven cases). Structural defects identifiable on MRI were present only in 20 per cent of patients with IHH. Bajaj, S., Ammini, A.C., Marwaha, R., Gulati, P., Khetarpal, K. & Mahajan, H. (1993). Clinical Radiology 48, 122-124. Magnetic Resonance Imaging of the Brain in Idiopathic Hypogonadotropic Hypogonadism
Accepted for Publication 2 February 1993
Idiopathic hypogonadotropic hypogonadism (IHH) is a disorder in which secretion of normal pulsatile gonadotropin releasing hormone (GnRH) from the hypothalamus is absent or abnormal [1]. A broad Spectrum of secretory patterns ranging from total absence to idiopathic loss of G n R H secretion after puberty has been described in I H H resulting in clinical heterogeneity [2]. The most common presentation is that of a complete absence of pubertal development with minimal testicular growth. Plasma luteinizing hormone (LH), follicle stimulatihg hormone (FSH) and testosterone are below the normal range. A more severely affected subgroup of these patients has hyposmia or anosmia, microphallus and undescended testes and is referred to as Kallmann's syndrome (KS). In these patients G n R H secretion may have been deficient in utero. Studies in experimental animals have demonstrated that GnRH-producing neurons originate in the olfactory tract. Defects in the pathways regulating the migration could account for the absence of G n R H secretion and the anosmia observed in these patients. Few anatomic studies have evaluated the hypothalamus, pituitary and olfactory region in I H H [4,5]. We report our experience with MRI of the brain in a series o f patients with IHH.
and computed tomography (CT) were performed to exclude a pituitary mass lesion. Serum T4, TSH and prolactin measurements were made in all cases. Olfaction was assessed by a qualitative evaluation of both detection and identification thresholds of the following odorants: camphoraceous (camphor), aromatic (clove oil), ethereal (spirit) and putrid (asafoetida), using two concentrations of solution: 1% and 0.01%. Patients who were unable to detect the odour at either concentration were defined as anosmic; and hyposmic if the odour was perceived at 1% but not 0.01% dilution. Local nasal pathology and sinusitis was excluded in all cases. Imaging was performed using a 1.5 T magnet system (Magnetom; Seimens, Germany) at the Institute of Nuclear Medicine and Allied Sciences. T1 (SE 700-400/ 22) and T2 (SE 2000/90) weighted images were obtained: 4 mm thick contiguous sagittal and coronal sections were obtained through the sella turcica and 5 mm thick contiguous axial sections through the region of the olfactory sulci. Imaging was also performed in 10 normal healthy volunteers. Statistical analysis of pituitary gland measurements was carried out by the Student's unpaired t-test. The Mann-Whitney test was used to compare the difference between the mean values o f olfactory sulci in the two groups.
MATERIALS AND M E T H O D S Forty patients with I H H attending the follow-up Endocrine Clinic of the All India Institute of Medical Sciences over a period o f 18 months were studied. The diagnosis of hypogonadotropic hypogonadism was based on failure to undergo spontaneous puberty by the age of 20 years, prepubertal serum testosterone/oestradiol levels and low serum concentrations o f L H and FSH. A detailed clinical examination was performed in all the cases to exclude systemic illness. Plain radiography of the skull Correspondenceto: Dr Sarita Bajaj,Assistant Professor,Department of Medicine, SRN Hospital, Allahabad-211001, India.
RESULTS Clinical details are outlined in Table 1. The sense of smell was absent in nine (of 40) patients. Three subjects could detect the undiluted odour, but not the diluted one and were designated hyposmic. Midline anomaly (extra central teeth) and undescended testes were noted in one case each. In normal subjects the mean (S.D.) pituitary gland measurements were 9.2 (1.4) mm in length and 6.2 (1.1) mm in height. In I H H the dimensions were 8.9 (1.6) mm and 5.2 (1.2) mm respectively. The difference between
123
MRI IMAGING OF BRAIN IN HYPOGONADISM Table 1 - Clinical data from 40 patients with hypogonadotropic hypogonadism
IHH (euosmic) KS (hyposmic/anosmic)
Mean age
(S.D.)
M: F
Mean height
(S.D.J
25.3 23.0
(4.8) (3.2)
25 : 2 I 1: 1
172 174
(7.3) (7.2)
s.D., Standard deviation; IHH, idiopathic hypogonadotropic hypogonadism; KS, Kallmann's syndrome.
rectus
/
Olfactory
,.
)d
9
rbital sulci
Olfactory sulcus
bulb and tract Fig. 1 - Schematic representation of a coronal section through the olfactory tract.
Fig. 3 - Axial T 1-weighted (SE 500/22) image showing bilaterally absent olfactory sulci.
Fig. 2 - T l-weighted (SE 410/22) axial image showing hypoplastic right olfactory sulcus. Arrows demonstrate normal olfactory sulcus on left side.
length and height of the pituitary gland in normal healthy volunteers and patients of I H H was not significant ( P > 0.05). Posterior pituitary bright signal was absent in nine cases and empty sella noted in seven. The stalk was normally visualized. Figure 1 shows a schematic representation of a coronal section through the olfactory tract. Average length and width o f the olfactory sulci in normal individuals was 42.6 (3.8) mm and 4.8 (1.0) mm respectively. Hypoplasia was observed in four cases (unilateral, two (Fig. 2); bilateral, two) and aplasia in two subjects (unilateral, one; bilateral, one (Fig. 3)). In one patient the sulcus was dystrophic on the right side and atrophic on the left. Markedly distorted shape was noted on the right side in one case, being normal on the left. Olfaction was impaired in all subjects with defective olfactory sulci.
Fig. 4 Axial Tl-weighted (SE 500/22) image through olfactory lobes showing normal bilateral olfactory sulci (arrows).
124
CLINICAL RADIOLOGY
The olfactory region was bilaterally symmetrical in the remaining 32 cases (Fig. 4). Measurements were not significantly different ( P > 0.05) from those of normal subjects (mean length 42.6 (3.8) ram, width 4.8 (1.0) mm, I H H , 38.8 (7.4) mm, 5.3 (0.8) m m respectively). DISCUSSION M R I by virtue of its superior tissue contrast and greater sensitivity has become the modality of choice for evaluating central nervous system a n a t o m y in vivo [6]. Pituitary gland size on M R I correlates with CT and autopsy findings, with a m6an height of 5.7 m m (range 3-9 mm) [7]. Average height and length o f the pituitary gland in adult subjects as reported by H a y a k a w a et al. [8] was 4.8+ 1.0 mm, 8.9_+ 1.1 m m for men and 6.0_+0.8 mm, 9.1 q-_1.1 m m for women respectively. The hyperintense region of the posterior part of the pituitary on Tl-weighted sagittal images corresponds anatomically to the posterior lobe of the gland [9]. Recent studies [6,9] have shown that it represents the neurohypophysis. Absence of the posterior pituitary signal is found in 10% of the healthy population [6]. A partially empty sella is a very c o m m o n incidental finding and a complete absence of tl~e diaphragma sella is present in 5% of normal subjects. Unilaterally or bilaterally absent olfactory lobes have been documented on post-mortem examination of patients with Kallmann's syndrome (KS) [4]. Kovacs and Sheehan [5] found marked histologic changes in the pituitary and hypothalamus o f a patient of KS. Lieblich et al. [10] demonstrated absent olfactory sulci in four of 23 patients of KS who underwent pneumoencephalography. The rhinencephalon, however, could not be demonstrated in euosmic men. C T and M R I have failed to demonstrate associated abnormalities within the hypothalamic-pituitary region in H-IH [3]. Klingmuller et al. [4] performed M R I in five euosmic men with I H H , four men with KS and five normal men. In normal and I H H men, the olfactory sulci were visualized as 3-5 m m thick, approximately 40 m m tong grey bands. Some d e g r e e ' o f abnormality was observed in all the four patients of KS in the form of hypoplasia (one case), aplasia or rudimentary sulci (three cases). In our study, mean length and height of the pituitary gland in healthy individuals was similar to that reported in the literature [8]. Differences observed between normal subjects and patients o f I H H regarding pituitary hypothalamic dimensions were not statistically significant. In control cases and euosmic I H H axial sections of the
brain revealed olfactory sulci of comparable length and width to those described by Klingmuller et al. [4]. Axial images of the olfactory region demonstrated a range of defects in the majority (8/12) o f cases o f KS (one hyp0smic, seven anosmic). However, four subjects o f KS (two hyposmic, two anosmic) had normal olfactory sulci in contrast to the observation ofKlingmuller et al. [4] who documented varying degrees of defects in all four cases of KS imaged. M R I revealed structural defects in the rhinencephalon in the majority o f subjects with Kallmann's syndrome explaining the anosmia. A subset did not show any macroscopic olfactory lobe lesion. This suggests a microscopic or functional abnormality. We have shown that M R I of the pituitary and hypothalamus did not show an abnormality in I H H but structural lesions o f the rhinencephalon were found in 67% of patients with impaired olfaction.
REFERENCES
I Hoffman AR, Crowley WF. Induction of puberty in men by long term pulsatile administration of low dose gonadotropin releasing hormone. New England Journal of Medicine 1982;307:1237-1241. 2 Crowley WF, Whitcomb RW. Gonadotropin-releasing hormone deficiencyin men: diagnosis andtreatment with exogenousgonadotropin-releasing hormone. American Journal of Obstetrics and Gynecology 1990;163:1752-1758. 3 Whitcomb RW, Crowley WF. Diagnosis and treatment of isolated gonadotropin-releasing hormone deficiency in men. Journal of Clinical Endocrinology and Metabolism 1990;70:3-7. 4 Klingmuller D, Dewes W, Krahe T, Brecht L, Schweikert H-U. Magnetic resonance imaging of the brain in patients with anosmia and hypothalamic hypogonadism (Kallmann's syndrome). Journal of Clinical Endocrinology and Metabolism 1987;65:581-584. 5 Kovacs K, Sheehan HL. Pituitary changes in Kallmann's syndrome: a histologicimmunocytologic,ultrastructural, and immunoelectron microscopic study. Fertility and Sterility 1982;37:83-89. 6 Chakeres DW, Curtin A, Ford G. Magnetic resonance imaging of pituitary and parasellar abnormalities. Radiologic Clinics of North America 1989;27:265-281. 7 Mark L, Peck P, Daniels D, Charles C, William A, Haughton VM. The pituitary fossa:a correlativeanatomic and MR study. Radiology 1984;153:453457. 8 Hayakawa K; Konishi Y, Matsuda T, Kuriyama M, Konishi K, Yamashita K et al. Development and aging of brain midline structures: assessmentwith MR imaging. Radiology 1989;172:171177. 9 Colombo N, Berry I, Kucharczyk J, Kucharczyk W, de Groot J, Larson T et al. Posterior pituitary gland: appearance on MR images in normal and pathologic states. Radiology 1987;165:481-485. 10 Lieblich JM, Rogol AD, White BJ, Rosen SW. Syndrome of anosmia with hypogonadotropic hypogonadism (Kallmann syndrome). American Journal of Medicine 1982;73:506 519.
Magnetic Resonance Imaging of the Brain in Idiopathic Hypogonadotropic Hypogonadism S. BAJAJ, A. C. A M M I N I * , R. M A R W A H A t , P. G U L A T I t , K. KHETARPAL:~ and H. MAHAJANw
Department of Medicine, SRN Hospital, Allahabad, *Department of Endocrinology, Metabolism and Diabetes, Ansari Nagar, New Delhi, tDepartment of Radiology, NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, New Delhi, ~Department of Physiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, and w Institute of Imaging and Research, New Delhi, India Magnetic resonance imaging (MRI) of the pituitary, hypothalamus and olfactory sulci was performed in 40 patients with idiopathic hypogonadotropic hypogonadism (IHH). Twelve of these patients had an impaired sense of smell (Kallmann's syndrome). Sagittai and coronal imaging revealed no morphological abnormalities in the hypothalamic-pituitary region. On axial imaging rudimentary, hypoplastic or aplastic olfactory sulci were found in eight cases. All patients with olfactory sulcai abnormalities had associated hyposmia (one case) or anosmia (seven cases). Structural defects identifiable on MRI were present only in 20 per cent of patients with IHH. Bajaj, S., Ammini, A.C., Marwaha, R., Gulati, P., Khetarpal, K. & Mahajan, H. (1993). Clinical Radiology 48, 122-124. Magnetic Resonance Imaging of the Brain in Idiopathic Hypogonadotropic Hypogonadism
Accepted for Publication 2 February 1993
Idiopathic hypogonadotropic hypogonadism (IHH) is a disorder in which secretion of normal pulsatile gonadotropin releasing hormone (GnRH) from the hypothalamus is absent or abnormal [1]. A broad Spectrum of secretory patterns ranging from total absence to idiopathic loss of G n R H secretion after puberty has been described in I H H resulting in clinical heterogeneity [2]. The most common presentation is that of a complete absence of pubertal development with minimal testicular growth. Plasma luteinizing hormone (LH), follicle stimulatihg hormone (FSH) and testosterone are below the normal range. A more severely affected subgroup of these patients has hyposmia or anosmia, microphallus and undescended testes and is referred to as Kallmann's syndrome (KS). In these patients G n R H secretion may have been deficient in utero. Studies in experimental animals have demonstrated that GnRH-producing neurons originate in the olfactory tract. Defects in the pathways regulating the migration could account for the absence of G n R H secretion and the anosmia observed in these patients. Few anatomic studies have evaluated the hypothalamus, pituitary and olfactory region in I H H [4,5]. We report our experience with MRI of the brain in a series o f patients with IHH.
and computed tomography (CT) were performed to exclude a pituitary mass lesion. Serum T4, TSH and prolactin measurements were made in all cases. Olfaction was assessed by a qualitative evaluation of both detection and identification thresholds of the following odorants: camphoraceous (camphor), aromatic (clove oil), ethereal (spirit) and putrid (asafoetida), using two concentrations of solution: 1% and 0.01%. Patients who were unable to detect the odour at either concentration were defined as anosmic; and hyposmic if the odour was perceived at 1% but not 0.01% dilution. Local nasal pathology and sinusitis was excluded in all cases. Imaging was performed using a 1.5 T magnet system (Magnetom; Seimens, Germany) at the Institute of Nuclear Medicine and Allied Sciences. T1 (SE 700-400/ 22) and T2 (SE 2000/90) weighted images were obtained: 4 mm thick contiguous sagittal and coronal sections were obtained through the sella turcica and 5 mm thick contiguous axial sections through the region of the olfactory sulci. Imaging was also performed in 10 normal healthy volunteers. Statistical analysis of pituitary gland measurements was carried out by the Student's unpaired t-test. The Mann-Whitney test was used to compare the difference between the mean values o f olfactory sulci in the two groups.
MATERIALS AND M E T H O D S Forty patients with I H H attending the follow-up Endocrine Clinic of the All India Institute of Medical Sciences over a period o f 18 months were studied. The diagnosis of hypogonadotropic hypogonadism was based on failure to undergo spontaneous puberty by the age of 20 years, prepubertal serum testosterone/oestradiol levels and low serum concentrations o f L H and FSH. A detailed clinical examination was performed in all the cases to exclude systemic illness. Plain radiography of the skull Correspondenceto: Dr Sarita Bajaj,Assistant Professor,Department of Medicine, SRN Hospital, Allahabad-211001, India.
RESULTS Clinical details are outlined in Table 1. The sense of smell was absent in nine (of 40) patients. Three subjects could detect the undiluted odour, but not the diluted one and were designated hyposmic. Midline anomaly (extra central teeth) and undescended testes were noted in one case each. In normal subjects the mean (S.D.) pituitary gland measurements were 9.2 (1.4) mm in length and 6.2 (1.1) mm in height. In I H H the dimensions were 8.9 (1.6) mm and 5.2 (1.2) mm respectively. The difference between
123
MRI IMAGING OF BRAIN IN HYPOGONADISM Table 1 - Clinical data from 40 patients with hypogonadotropic hypogonadism
IHH (euosmic) KS (hyposmic/anosmic)
Mean age
(S.D.)
M: F
Mean height
(S.D.J
25.3 23.0
(4.8) (3.2)
25 : 2 I 1: 1
172 174
(7.3) (7.2)
s.D., Standard deviation; IHH, idiopathic hypogonadotropic hypogonadism; KS, Kallmann's syndrome.
rectus
/
Olfactory
,.
)d
9
rbital sulci
Olfactory sulcus
bulb and tract Fig. 1 - Schematic representation of a coronal section through the olfactory tract.
Fig. 3 - Axial T 1-weighted (SE 500/22) image showing bilaterally absent olfactory sulci.
Fig. 2 - T l-weighted (SE 410/22) axial image showing hypoplastic right olfactory sulcus. Arrows demonstrate normal olfactory sulcus on left side.
length and height of the pituitary gland in normal healthy volunteers and patients of I H H was not significant ( P > 0.05). Posterior pituitary bright signal was absent in nine cases and empty sella noted in seven. The stalk was normally visualized. Figure 1 shows a schematic representation of a coronal section through the olfactory tract. Average length and width o f the olfactory sulci in normal individuals was 42.6 (3.8) mm and 4.8 (1.0) mm respectively. Hypoplasia was observed in four cases (unilateral, two (Fig. 2); bilateral, two) and aplasia in two subjects (unilateral, one; bilateral, one (Fig. 3)). In one patient the sulcus was dystrophic on the right side and atrophic on the left. Markedly distorted shape was noted on the right side in one case, being normal on the left. Olfaction was impaired in all subjects with defective olfactory sulci.
Fig. 4 Axial Tl-weighted (SE 500/22) image through olfactory lobes showing normal bilateral olfactory sulci (arrows).
124
CLINICAL RADIOLOGY
The olfactory region was bilaterally symmetrical in the remaining 32 cases (Fig. 4). Measurements were not significantly different ( P > 0.05) from those of normal subjects (mean length 42.6 (3.8) ram, width 4.8 (1.0) mm, I H H , 38.8 (7.4) mm, 5.3 (0.8) m m respectively). DISCUSSION M R I by virtue of its superior tissue contrast and greater sensitivity has become the modality of choice for evaluating central nervous system a n a t o m y in vivo [6]. Pituitary gland size on M R I correlates with CT and autopsy findings, with a m6an height of 5.7 m m (range 3-9 mm) [7]. Average height and length o f the pituitary gland in adult subjects as reported by H a y a k a w a et al. [8] was 4.8+ 1.0 mm, 8.9_+ 1.1 m m for men and 6.0_+0.8 mm, 9.1 q-_1.1 m m for women respectively. The hyperintense region of the posterior part of the pituitary on Tl-weighted sagittal images corresponds anatomically to the posterior lobe of the gland [9]. Recent studies [6,9] have shown that it represents the neurohypophysis. Absence of the posterior pituitary signal is found in 10% of the healthy population [6]. A partially empty sella is a very c o m m o n incidental finding and a complete absence of tl~e diaphragma sella is present in 5% of normal subjects. Unilaterally or bilaterally absent olfactory lobes have been documented on post-mortem examination of patients with Kallmann's syndrome (KS) [4]. Kovacs and Sheehan [5] found marked histologic changes in the pituitary and hypothalamus o f a patient of KS. Lieblich et al. [10] demonstrated absent olfactory sulci in four of 23 patients of KS who underwent pneumoencephalography. The rhinencephalon, however, could not be demonstrated in euosmic men. C T and M R I have failed to demonstrate associated abnormalities within the hypothalamic-pituitary region in H-IH [3]. Klingmuller et al. [4] performed M R I in five euosmic men with I H H , four men with KS and five normal men. In normal and I H H men, the olfactory sulci were visualized as 3-5 m m thick, approximately 40 m m tong grey bands. Some d e g r e e ' o f abnormality was observed in all the four patients of KS in the form of hypoplasia (one case), aplasia or rudimentary sulci (three cases). In our study, mean length and height of the pituitary gland in healthy individuals was similar to that reported in the literature [8]. Differences observed between normal subjects and patients o f I H H regarding pituitary hypothalamic dimensions were not statistically significant. In control cases and euosmic I H H axial sections of the
brain revealed olfactory sulci of comparable length and width to those described by Klingmuller et al. [4]. Axial images of the olfactory region demonstrated a range of defects in the majority (8/12) o f cases o f KS (one hyp0smic, seven anosmic). However, four subjects o f KS (two hyposmic, two anosmic) had normal olfactory sulci in contrast to the observation ofKlingmuller et al. [4] who documented varying degrees of defects in all four cases of KS imaged. M R I revealed structural defects in the rhinencephalon in the majority o f subjects with Kallmann's syndrome explaining the anosmia. A subset did not show any macroscopic olfactory lobe lesion. This suggests a microscopic or functional abnormality. We have shown that M R I of the pituitary and hypothalamus did not show an abnormality in I H H but structural lesions o f the rhinencephalon were found in 67% of patients with impaired olfaction.
REFERENCES
I Hoffman AR, Crowley WF. Induction of puberty in men by long term pulsatile administration of low dose gonadotropin releasing hormone. New England Journal of Medicine 1982;307:1237-1241. 2 Crowley WF, Whitcomb RW. Gonadotropin-releasing hormone deficiencyin men: diagnosis andtreatment with exogenousgonadotropin-releasing hormone. American Journal of Obstetrics and Gynecology 1990;163:1752-1758. 3 Whitcomb RW, Crowley WF. Diagnosis and treatment of isolated gonadotropin-releasing hormone deficiency in men. Journal of Clinical Endocrinology and Metabolism 1990;70:3-7. 4 Klingmuller D, Dewes W, Krahe T, Brecht L, Schweikert H-U. Magnetic resonance imaging of the brain in patients with anosmia and hypothalamic hypogonadism (Kallmann's syndrome). Journal of Clinical Endocrinology and Metabolism 1987;65:581-584. 5 Kovacs K, Sheehan HL. Pituitary changes in Kallmann's syndrome: a histologicimmunocytologic,ultrastructural, and immunoelectron microscopic study. Fertility and Sterility 1982;37:83-89. 6 Chakeres DW, Curtin A, Ford G. Magnetic resonance imaging of pituitary and parasellar abnormalities. Radiologic Clinics of North America 1989;27:265-281. 7 Mark L, Peck P, Daniels D, Charles C, William A, Haughton VM. The pituitary fossa:a correlativeanatomic and MR study. Radiology 1984;153:453457. 8 Hayakawa K; Konishi Y, Matsuda T, Kuriyama M, Konishi K, Yamashita K et al. Development and aging of brain midline structures: assessmentwith MR imaging. Radiology 1989;172:171177. 9 Colombo N, Berry I, Kucharczyk J, Kucharczyk W, de Groot J, Larson T et al. Posterior pituitary gland: appearance on MR images in normal and pathologic states. Radiology 1987;165:481-485. 10 Lieblich JM, Rogol AD, White BJ, Rosen SW. Syndrome of anosmia with hypogonadotropic hypogonadism (Kallmann syndrome). American Journal of Medicine 1982;73:506 519.